Alzheimer DiseasePhase 1NCT02769065
Study of TAK-071 in Healthy Participants and Participants With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability (BA) and Food Effect of TAK-071 in Healthy Participants
A Phase 1 study testing TAK-071 and Donepezil in people with Alzheimer Disease and Healthy Volunteers, run by Takeda at 1 site in United States.
Trial summary
The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally in healthy participants and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD). Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Healthy Volunteers
- What is being tested?
- TAK-071 and Donepezil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 179 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2016to 8 Jun 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years, inclusive (nonelderly at the time of informed consent and first study drug dose) for Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55 to 90 years, inclusive, for participants in Cohort 16.
- For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in Japan of Japanese parents and Japanese grandparents and living no more than 10 years outside of Japan, with no significant change in lifestyle, including diet, while living outside of Japan.
- Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26 inclusive, respectively, and no biomarker data to contradict this diagnosis. Participants with documented diagnosis of MCI or mild AD must be receiving ongoing donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in (Day -1) or must consent to take donepezil dose titrated to at least 21 days of treatment with 10 mg QD prior to Check-in.
Who cannot join
- Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16) neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.
- Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to 15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled (hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in the study.
- Has a risk of suicide or suicidal ideation with intent and plan according to the investigator's clinical judgment (affirmative answer to questions 4 and 5 of the ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.
- Cohort 16 only: Any significant neurologic disease (other than suspected incipient or mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct dementia, Huntington disease, head trauma with clinically significant cognitive sequelae, or chronic central nervous system infection, per investigator discretion.
- Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption [eg, bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per week] occurrence of heartburn).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Oral Doses of TAK-071 in Healthy Subjects and Subjects With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability and Food Effect of TAK-071 in Healthy Subjects
The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally in healthy participants and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD).
Read the detailed description
TAK-071 was being tested to find a safe and well-tolerated dose in healthy participants (non-Japanese and Japanese) and participants with MCI or mild AD (non-Japanese).
The study enrolled 179 participants. The study consisted of 4 parts: Single-rising dose (SRD) part (Cohorts 1-6, and 18-22), multiple-rising dose (MRD) part (Cohorts 7-15), Cohort 16 with 2-arm parallel design, and Cohort 17 relative bioavailability and food effect 3 period crossover design.
Participants in each cohort were randomized to receive treatment with TAK-071 or matching placebo using drug-in-capsule (DIC) in the morning following a minimum fast of 8 hours. In Cohort 16, participants were assigned to 1 of 2 possible treatments, TAK-071 or matching placebo. In Cohort 17, participants were assigned to 1 of 3 treatment sequences (ABC, BCA, or CAB) with treatment A being fasted state and capsule formulation, treatment B being fasted state and tablet formulation, and treatment C being fed state and tablet formulation. In Cohorts 20-22, participants were administered as a single dose of TAK-071 or placebo on Day 1, and a single dose of donepezil or placebo approximately 24 hours later on Day 2.
This multi-center trial was conducted in United States. The overall time to participate in this study was approximately 41 days. Participants made multiple visits to the clinic and were also contacted for the follow-up through the telephone.
- Conditions
- Alzheimer Disease, Healthy Volunteers
- Being tested
- TAK-071, Donepezil, TAK-071 Placebo, Donepezil Placebo
- Keywords
- Drug Therapy
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-071Drug
TAK-071 capsules
DonepezilDrug
Donepezil over-encapsulated tablet
TAK-071 PlaceboDrug
TAK-071 placebo-matching capsules
Donepezil PlaceboDrug
Donepezil placebo-matching over-encapsulated tablet
| Study group | Role | What they receive |
|---|---|---|
| SRD: Placebo Cohorts 1-6, 18 and 19 | Placebo comparator | TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. Receives: Drug: TAK-071 Placebo |
| SRD: Cohort 1: TAK-071 1 mg | Experimental | TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. Receives: Drug: TAK-071 |
| SRD: Cohort 2: TAK-071 3 mg | Experimental | TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. Receives: Drug: TAK-071 |
| SRD: Cohort 3: TAK-071 9 mg | Experimental | TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. Receives: Drug: TAK-071 |
| SRD: Cohort 4: TAK-071 20 mg | Experimental | TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. Receives: Drug: TAK-071 |
| SRD: Cohort 5: TAK-071 40 mg | Experimental | TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. Receives: Drug: TAK-071 |
| SRD: Cohort 6: TAK-071 80 mg | Experimental | TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 Receives: Drug: TAK-071 |
| MRD: Placebo Cohorts 7-9 | Placebo comparator | TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. Receives: Drug: TAK-071 Placebo |
| MRD: Cohort 7: TAK-071 3 mg | Experimental | TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. Receives: Drug: TAK-071 |
| MRD: Cohort 8: TAK-071 9 mg | Experimental | TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. Receives: Drug: TAK-071 |
| MRD: Cohort 9: TAK-071 15 mg | Experimental | TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. Receives: Drug: TAK-071 |
| MRD: TAK-071 Placebo Cohorts 10-12+Donepezil | Placebo comparator | TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Receives: Drug: Donepezil; Drug: TAK-071 Placebo |
| MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg | Experimental | TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. Receives: Drug: TAK-071; Drug: Donepezil |
| MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg | Experimental | TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. Receives: Drug: TAK-071; Drug: Donepezil |
| MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg | Experimental | TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. Receives: Drug: TAK-071; Drug: Donepezil |
| MRD: Placebo Cohorts 13-15 | Experimental | TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. Receives: Drug: TAK-071 Placebo |
| MRD: Cohort 13: TAK-071 3 mg | Experimental | TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. Receives: Drug: TAK-071 |
| MRD: Cohort 14: TAK-071 9 mg | Experimental | TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. Receives: Drug: TAK-071 |
| MRD: Cohort 15: TAK-071 15 mg | Experimental | TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. Receives: Drug: TAK-071 |
| Cohort 16 | Experimental | Not described Receives: Drug: TAK-071 |
| Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC | Experimental | A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. Receives: Drug: TAK-071 |
| BA/Food Effect: Cohort 17 Sequence BCA | Experimental | B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. Receives: Drug: TAK-071 |
| BA/Food Effect: Cohort 17 Sequence CAB | Experimental | C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. Receives: Drug: TAK-071 |
| SRD: Cohort 18: TAK-071 120 mg | Experimental | TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. Receives: Drug: TAK-071 |
| SRD: Cohort 19: TAK-071 160 mg | Experimental | TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. Receives: Drug: TAK-071 |
| SRD: TAK-071 Placebo+Donepezil Placebo | Placebo comparator | TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. Receives: Drug: TAK-071 Placebo; Drug: Donepezil Placebo |
| SRD: TAK-071 Placebo+Donepezil | Placebo comparator | TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. Receives: Drug: Donepezil; Drug: TAK-071 Placebo |
| SRD: Cohort 20: TAK-071 40 mg+Donepezil | Experimental | TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. Receives: Drug: TAK-071; Drug: Donepezil |
| SRD: Cohort 21: TAK-071 60 mg+Donepezil | Experimental | TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. Receives: Drug: TAK-071; Drug: Donepezil |
| SRD: Cohort 22: TAK-071 80 mg+Donepizil | Experimental | TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21. Receives: Drug: TAK-071; Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs or gets worse after receiving study drug.
Measured: Day 1 up to Day 41
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post-dose
Clinical laboratory tests included serum chemistry, hematology, coagulation and urinalysis. ULN=upper limit of normal range.
Measured: Day 1 up to Day 41
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Vital Sign measurements included systolic blood pressure (SBP), diastolic blood presssure (DBP), pulse, temperature, orthostatic SBP, orthostatic DBP and orthostatic pulse.
Measured: Day 1 up to Day 41
Percentage of Participants Who Meet the Markedly Abnormal Criteria for 12-lead Electrocardiogram (ECG) Parameters at Least Once Post-dose
A standard 12-lead electrocardiogram (ECG) was performed. The percentage of participants with markedly abnormal ECG findings during the study.
Measured: Day 1 up to Day 41
Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]
Measured: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]
Measured: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21]
Measured: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8]
Measured: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28]
Measured: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Measured: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Measured: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Secondary outcomes (41)
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and multiple timepoints (up to 24 hrs) post-dose for Cohorts 7 and 8 and Pre-dose on Day 1 and multiple timepoints (up to 96 hrs) post-dose for Cohort 9
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose and Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese
Measured: Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Measured: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Measured: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8, and pre-dose on Day 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants
Measured: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 multiple time points (up to 96 hours) post-dose for Cohort 9
CLR: Renal Clearance for TAK-071 MRD Japanese Participants
Measured: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Measured: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Measured: Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose
CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071
Measured: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071
Measured: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071
Measured: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071
Measured: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants
Measured: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants
Measured: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil
Measured: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Ratio of Geometric Mean of Cmax for Donepezil After 21 Daily Doses of TAK-071
A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.
Measured: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Ratio of Geometric Mean of AUC(0-24) for Donepezil After 21 Daily Doses of TAK-071
A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.
Measured: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start5 May 2016
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Why it stopped: Terminated prematurely as data from cohort no longer needed due to indication change.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02769065
- Sponsor's protocol ID
- TAK-071-1001
- Other IDs
- U1111-1176-7435
- Status last verified
- Mar 2019
- First submitted
- 10 May 2016
- Last updated
- 10 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Oral Doses of TAK-071 in Healthy Subjects and Subjects With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability and Food Effect of TAK-071 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02769065
- Acronym / sponsor ID
- TAK-071-1001
- Conditions
- Alzheimer Disease, Healthy Volunteers
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prematurely as data from cohort no longer needed due to indication change.
- Enrolment
- 179 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 5 May 2016 (actual)
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 11 May 2016 (estimated)
- Results
- Posted 10 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally in healthy participants and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD).
Detailed description
TAK-071 was being tested to find a safe and well-tolerated dose in healthy participants (non-Japanese and Japanese) and participants with MCI or mild AD (non-Japanese).
The study enrolled 179 participants. The study consisted of 4 parts: Single-rising dose (SRD) part (Cohorts 1-6, and 18-22), multiple-rising dose (MRD) part (Cohorts 7-15), Cohort 16 with 2-arm parallel design, and Cohort 17 relative bioavailability and food effect 3 period crossover design.
Participants in each cohort were randomized to receive treatment with TAK-071 or matching placebo using drug-in-capsule (DIC) in the morning following a minimum fast of 8 hours. In Cohort 16, participants were assigned to 1 of 2 possible treatments, TAK-071 or matching placebo. In Cohort 17, participants were assigned to 1 of 3 treatment sequences (ABC, BCA, or CAB) with treatment A being fasted state and capsule formulation, treatment B being fasted state and tablet formulation, and treatment C being fed state and tablet formulation. In Cohorts 20-22, participants were administered as a single dose of TAK-071 or placebo on Day 1, and a single dose of donepezil or placebo approximately 24 hours later on Day 2.
This multi-center trial was conducted in United States. The overall time to participate in this study was approximately 41 days. Participants made multiple visits to the clinic and were also contacted for the follow-up through the telephone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 30
| Arm | Type | Receives |
|---|---|---|
| SRD: Placebo Cohorts 1-6, 18 and 19 | Placebo comparator | Drug: TAK-071 PlaceboTAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period. |
| SRD: Cohort 1: TAK-071 1 mg | Experimental | Drug: TAK-071TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants. |
| SRD: Cohort 2: TAK-071 3 mg | Experimental | Drug: TAK-071TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1. |
| SRD: Cohort 3: TAK-071 9 mg | Experimental | Drug: TAK-071TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data. |
| SRD: Cohort 4: TAK-071 20 mg | Experimental | Drug: TAK-071TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort. |
| SRD: Cohort 5: TAK-071 40 mg | Experimental | Drug: TAK-071TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4. |
| SRD: Cohort 6: TAK-071 80 mg | Experimental | Drug: TAK-071TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5 |
| MRD: Placebo Cohorts 7-9 | Placebo comparator | Drug: TAK-071 PlaceboTAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period. |
| MRD: Cohort 7: TAK-071 3 mg | Experimental | Drug: TAK-071TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3. |
| MRD: Cohort 8: TAK-071 9 mg | Experimental | Drug: TAK-071TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. |
| MRD: Cohort 9: TAK-071 15 mg | Experimental | Drug: TAK-071TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort. |
| MRD: TAK-071 Placebo Cohorts 10-12+Donepezil | Placebo comparator | Drug: Donepezil, Drug: TAK-071 PlaceboTAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. |
| MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7. |
| MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8. |
| MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9. |
| MRD: Placebo Cohorts 13-15 | Experimental | Drug: TAK-071 PlaceboTAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants. |
| MRD: Cohort 13: TAK-071 3 mg | Experimental | Drug: TAK-071TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7. |
| MRD: Cohort 14: TAK-071 9 mg | Experimental | Drug: TAK-071TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8. |
| MRD: Cohort 15: TAK-071 15 mg | Experimental | Drug: TAK-071TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9. |
| Cohort 16 | Experimental | Drug: TAK-071 |
| Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC | Experimental | Drug: TAK-071A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. |
| BA/Food Effect: Cohort 17 Sequence BCA | Experimental | Drug: TAK-071B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. |
| BA/Food Effect: Cohort 17 Sequence CAB | Experimental | Drug: TAK-071C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period. |
| SRD: Cohort 18: TAK-071 120 mg | Experimental | Drug: TAK-071TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6. |
| SRD: Cohort 19: TAK-071 160 mg | Experimental | Drug: TAK-071TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18. |
| SRD: TAK-071 Placebo+Donepezil Placebo | Placebo comparator | Drug: TAK-071 Placebo, Drug: Donepezil PlaceboTAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants. |
| SRD: TAK-071 Placebo+Donepezil | Placebo comparator | Drug: Donepezil, Drug: TAK-071 PlaceboTAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants. |
| SRD: Cohort 20: TAK-071 40 mg+Donepezil | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19. |
| SRD: Cohort 21: TAK-071 60 mg+Donepezil | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20. |
| SRD: Cohort 22: TAK-071 80 mg+Donepizil | Experimental | Drug: TAK-071, Drug: DonepezilTAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years, inclusive (nonelderly at the time of informed consent and first study drug dose) for Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55 to 90 years, inclusive, for participants in Cohort 16.
- For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in Japan of Japanese parents and Japanese grandparents and living no more than 10 years outside of Japan, with no significant change in lifestyle, including diet, while living outside of Japan.
- Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26 inclusive, respectively, and no biomarker data to contradict this diagnosis. Participants with documented diagnosis of MCI or mild AD must be receiving ongoing donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in (Day -1) or must consent to take donepezil dose titrated to at least 21 days of treatment with 10 mg QD prior to Check-in.
Key exclusion criteria (5 listed)
- Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16) neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.
- Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to 15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled (hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in the study.
- Has a risk of suicide or suicidal ideation with intent and plan according to the investigator's clinical judgment (affirmative answer to questions 4 and 5 of the ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.
- Cohort 16 only: Any significant neurologic disease (other than suspected incipient or mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct dementia, Huntington disease, head trauma with clinically significant cognitive sequelae, or chronic central nervous system infection, per investigator discretion.
- Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption [eg, bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per week] occurrence of heartburn).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-071TAK-071 capsules | Drug | BA/Food Effect: Cohort 17 Sequence BCA, BA/Food Effect: Cohort 17 Sequence CAB, Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC, Cohort 16, MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg, MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg, MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg, MRD: Cohort 13: TAK-071 3 mg, MRD: Cohort 14: TAK-071 9 mg, MRD: Cohort 15: TAK-071 15 mg, MRD: Cohort 7: TAK-071 3 mg, MRD: Cohort 8: TAK-071 9 mg, MRD: Cohort 9: TAK-071 15 mg, SRD: Cohort 18: TAK-071 120 mg, SRD: Cohort 19: TAK-071 160 mg, SRD: Cohort 1: TAK-071 1 mg, SRD: Cohort 20: TAK-071 40 mg+Donepezil, SRD: Cohort 21: TAK-071 60 mg+Donepezil, SRD: Cohort 22: TAK-071 80 mg+Donepizil, SRD: Cohort 2: TAK-071 3 mg, SRD: Cohort 3: TAK-071 9 mg, SRD: Cohort 4: TAK-071 20 mg, SRD: Cohort 5: TAK-071 40 mg, SRD: Cohort 6: TAK-071 80 mg |
| DonepezilDonepezil over-encapsulated tablet | Drug | MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg, MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg, MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg, MRD: TAK-071 Placebo Cohorts 10-12+Donepezil, SRD: Cohort 20: TAK-071 40 mg+Donepezil, SRD: Cohort 21: TAK-071 60 mg+Donepezil, SRD: Cohort 22: TAK-071 80 mg+Donepizil, SRD: TAK-071 Placebo+Donepezil |
| TAK-071 PlaceboTAK-071 placebo-matching capsules | Drug | MRD: Placebo Cohorts 13-15, MRD: Placebo Cohorts 7-9, MRD: TAK-071 Placebo Cohorts 10-12+Donepezil, SRD: Placebo Cohorts 1-6, 18 and 19, SRD: TAK-071 Placebo+Donepezil, SRD: TAK-071 Placebo+Donepezil Placebo |
| Donepezil PlaceboDonepezil placebo-matching over-encapsulated tablet | Drug | SRD: TAK-071 Placebo+Donepezil Placebo |
Primary outcome
Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Day 1 up to Day 41
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs or gets worse after receiving study drug.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post-dose
Time frame: Day 1 up to Day 41
Clinical laboratory tests included serum chemistry, hematology, coagulation and urinalysis. ULN=upper limit of normal range.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Time frame: Day 1 up to Day 41
Vital Sign measurements included systolic blood pressure (SBP), diastolic blood presssure (DBP), pulse, temperature, orthostatic SBP, orthostatic DBP and orthostatic pulse.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for 12-lead Electrocardiogram (ECG) Parameters at Least Once Post-dose
Time frame: Day 1 up to Day 41
A standard 12-lead electrocardiogram (ECG) was performed. The percentage of participants with markedly abnormal ECG findings during the study.
Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]
Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]
Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21]
Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8]
Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28]
Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]
Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
41 secondary outcomes
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and multiple timepoints (up to 24 hrs) post-dose for Cohorts 7 and 8 and Pre-dose on Day 1 and multiple timepoints (up to 96 hrs) post-dose for Cohort 9
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose and Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese
Time frame: Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect
Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil
Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8, and pre-dose on Day 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9
AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9
Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants
Time frame: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 multiple time points (up to 96 hours) post-dose for Cohort 9
CLR: Renal Clearance for TAK-071 MRD Japanese Participants
Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Time frame: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071
Time frame: Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose
CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071
Time frame: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071
Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071
Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071
Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants
Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants
Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil
Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Ratio of Geometric Mean of Cmax for Donepezil After 21 Daily Doses of TAK-071
Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-071 and Donepezil in people with Alzheimer Disease and Healthy Volunteers, run by Takeda at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) (time frame: Day 1 up to Day 41). The study lists 42 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.