HealthyPhase 1NCT03224325
A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Multiple Doses of TAK-831 in Healthy Participants
A Phase 1 study testing TAK-831 Tablet T2 and TAK-831 Suspension in people with Healthy, run by Neurocrine Biosciences at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of TAK-831 when administered as multiple oral doses at escalating dose levels in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- TAK-831 Tablet T2 and TAK-831 Suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2017to 9 Sep 2018
- Phase
- Phase 1
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Has at least 45 kg weight and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.
- The participant is a healthy male or female not of childbearing potential adult who is aged 18 to 55 years, inclusive, at the time of informed consent and first study drug dose.
- A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days plus half-lives (95 days) after last study drug dose.
- A female participant with no childbearing potential, defined as a participant that has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who is postmenopausal (defined as continuous amenorrhea of at least 12 months and follicle stimulating hormone [FSH] greater than [>] 40 international unit per liter [IU/L]).
Who cannot join
- Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in.
- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as >3 drinks per day) within 5 years before the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. (1 drink=12 ounce [oz]. beer=5 oz. wine=1.5 oz. liquor.)
- Has a QT interval with Fridericia's correction method (QTcF) >450 milliseconds (ms) (male participants) or >470 ms (female participants) or PR outside the range of 120 to 220 ms, confirmed with 1 repeat testing, at the Screening Visit or Check-in. When triplicate electrocardiogram (ECG) assessments are collected, the mean of the 3 QTcF and PR values should be used to assess this criterion.
- Has a positive test result for hepatitis B surface antigen (HBsAg), anti- human chorionic gonadotropin (HCV), or human immunodeficiency virus (HIV) antibody/antigen at Screening.
- Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days before Check-in. Cotinine test is positive at Screening or Check-in.
- Has poor peripheral venous access.
Show all 21Show fewer
- Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days before the first dose of study medication.
- Has a Screening or Check-in abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved and documented by signature by the principal investigator or designee.
- Has a supine blood pressure outside 90 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in.
- Has a resting heart rate outside 40 to 100 beats per minute confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (heart rate from the ECG does not apply).
- Has a risk of suicide according to the Investigator's clinical judgment (example, per Columbia-Suicide Severity Rating Scale [C-SSRS]), or has scored "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior", if this behavior occurred in the past 2 years.
- Additional Exclusion Criteria for Cohort(s) with cerebrospinal fluid (CSF) Collection:
- Has had CSF collection performed within 30 days before Check-in.
- Has a history of clinically significant back pain and/or injury.
- Has local infection at the puncture site.
- Has thrombocytopenia or other suspected bleeding tendencies noted before procedure.
- Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia.
- Has any focal neurological deficit that might suggest an increase in intracranial pressure.
- Has any abnormal findings on ophthalmological assessment/fundoscopy suggestive of raised intracranial pressure (that is, optic disc swelling/edema; (uncontrolled) hypertensive retinopathy).
- Suffers regularly from moderate to severe headaches requiring analgesics.
- Has lower spinal malformations (on physical examination or lumbar spine radiography), local spinal infection, or other abnormalities that would exclude lumbar puncture (LP).
Trial locations and contacts
1 site in 1 country.
United States1 site
California Clinical Trials Medical Group/PAREXEL
Glendale, California, 91206
About this study
Official title: A Randomized, Investigator and Subject Blinded, Sponsor Unblinded Placebo-Controlled Phase I Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Multiple Doses of TAK-831 in Healthy Subjects
The purpose of this study is to evaluate the safety and tolerability of TAK-831 when administered as multiple oral doses at escalating dose levels in healthy participants.
Read the detailed description
This study is a randomized, investigator and participant blinded, sponsor unblinded, placebo-controlled, study of the safety, tolerability and pharmacokinetics of TAK-831 in up to 48 healthy volunteers, with 8 subjects in each of the 6 cohorts.
In each cohort, participants will be randomized in a 3:1 ratio to receive TAK-831 or placebo. Two formulations, oral suspension and tablet will be tested in this study. Both blood and cerebrospinal fluid (CSF) samples will be collected from selected cohorts (CSF cohorts); for the rest of the cohorts, only blood samples will be collected (non-CSF cohorts).
This single-center trial will be conducted in the United States. The overall time to participate in this study is 58 days. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.
- Conditions
- Healthy
- Being tested
- TAK-831 Tablet T2, Placebo, TAK-831 Suspension
- Keywords
- Drug therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-831 Tablet T2Drug
Tak-831 tablets.
PlaceboDrug
TAK-831 placebo-matching suspension.
TAK-831 SuspensionDrug
TAK-831 Suspension.
| Study group | Role | What they receive |
|---|---|---|
| Placebo (Pooled) | Other | TAK-831 placebo-matching suspension, orally, once daily (QD) for up to Day 16. Receives: Drug: Placebo |
| TAK-831 100 mg | Experimental | TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16. Receives: Drug: TAK-831 Tablet T2 |
| TAK-831 300 mg | Experimental | TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16. Receives: Drug: TAK-831 Tablet T2 |
| TAK-831 600 mg | Experimental | TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16. Receives: Drug: TAK-831 Tablet T2 |
| TAK-831 15 mg | Experimental | TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16. Receives: Drug: TAK-831 Suspension |
| TAK-831 800 mg | Experimental | TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16. Receives: Drug: TAK-831 Suspension |
| TAK-831 1200 mg | Experimental | TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16. Receives: Drug: TAK-831 Suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced at Least 1 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. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug.
Measured: Baseline up to 30 days after the last dose (Up to 48 days)
Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose
Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as: alanine aminotransferase (ALT)>3.0 U/L*upper limit of normal(ULN), albumin<25 g/L, alkaline phosphatase >3.0 U/L*ULN, aspartate aminotransferase >3.0 U/L*ULN, bilirubin >3.42 umol/L creatinine >177umol/L, gamma glutamyl transferase (GGT) >3 U/L*ULN, glucose <2.8 mmol/L, >19.4 mmol/L, potassium<3 mmol/L, >6 mmol/L, sodium <130 mmol/L, >150 mmol/L, protein <0.8 g/L,* lower limit of normal (LLN), >1.2 g/L*ULN, erythrocytes <0.8 (10^12/L)*LLN, >1.2 (10^12/L)*ULN, hematocrit (%) <0.8*LLN, >1.2*ULN, hemoglobin <0.8 g/L*LLN, >1.2 g/L*ULN, leukocytes <0.5 (10^9/L)*LLN, >1.5 (10^9/L)*ULN, platelets <75(10^9/L), >600(10^9/L). Only categories with values have been reported.
Measured: Baseline up to 30 days after the last dose (Up to 48 days)
Percentage of Participants Who Met the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose
Vital signs included temperature, pulse rate and blood pressure. Markedly abnormal values during treatment period were categorized as: Pulse Rate (beats/min) <50->120, Systolic Blood Pressure (SBP) (mmHg) <85->180, Diastolic Blood Pressure (DBP) (mmHg) <50->110 and Temperature (degree centigrades) <35.6- >37.7.
Measured: Baseline up to 30 days after the last dose (Up to 48 days)
Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose
A 12-lead ECG was performed. Markedly abnormal values during treatment period were categorized as: ECG Mean Heart Rate (beats/min) <50->120, PR Interval, Aggregate (msec) <=80->=200, QRS Duration, Aggregate (msec) <=80->=180, QT Interval, Aggregate (msec) <=300->=460, QTcF Interval, Aggregate (msec) <=300->=500 OR >=30 change from baseline and >=450 milliseconds.
Measured: Baseline up to 30 days after the last dose (Up to 48 days)
Secondary outcomes (4)
Cmax: Maximum Observed Plasma Concentration for TAK-831
Measured: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Day 1
Cmax ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831
Measured: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Day 16
Tmax: Time of First Occurrence of Cmax for TAK-831
Measured: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Days 1 and 16
AUC0-24: Area Under the Plasma Concentration-time Curve During a Dosing Interval for TAK-831
Measured: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Days 1 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start21 Jul 2017
- Primary completion9 Sep 2018
- Study completion9 Sep 2018
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 HealthyStudies of the same condition, open and under way.
- More trials run by Neurocrine BiosciencesThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224325
- Sponsor's protocol ID
- TAK-831-1005
- Status last verified
- Jun 2021
- First submitted
- 18 Jul 2017
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No