Alzheimer DiseasePhase 1NCT04157712
Multiple Ascending Dose Study of ALZ-801
A Phase 1 study of Alzheimer Disease, run by Alzheon Inc. at 1 site in United Kingdom.
Trial summary
Phase I, single-center, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability, and pharmacokinetics (PK) in plasma and urine, of multiple ascending doses of ALZ-801 (capsule, Part 1; prototype tablet Part 2) and the primary metabolite in healthy male or female subjects. Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Sep 2015to 4 Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy males, and females
- Age: 50-75 years, Part 1; 60-75 years Part 2
- Females must be of non-childbearing potential
- Body Mass Index 18-35 kg/m squared;
- Vital signs normal for age: BP 90-160/40-90 mmHg; HR 50 to 90 bpm)
- No clinically significant electrocardiogram readings
Who cannot join
- Body weight < 50 kg
- History of any drug or alcohol abuse in the past 2 years
- Subjects known to have a creatinine clearance of <60 mL/min
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- History of clinically significant cardiovascular, pulmonary, chronic respiratory, renal, hepatic, GI, immunologic, endocrine, neurologic, psychiatric or thromboembolic disease
- History of metabolic disturbances;
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Quotient Clinical
Ruddington, Nottingham, NG11 6JS
About this study
Official title: A Phase I, Single Centre, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics in Plasma and Urine of Multiple Ascending Doses of ALZ-801 in Healthy Elderly Subjects
Phase I, single-center, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability, and pharmacokinetics (PK) in plasma and urine, of multiple ascending doses of ALZ-801 (capsule, Part 1; prototype tablet Part 2) and the primary metabolite in healthy male or female subjects.
Read the detailed description
The study was conducted in two parts:
Part 1 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of multiple doses of ALZ-801 capsule formulation in healthy elderly subjects.
Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female subjects aged 50 to 75 years, inclusive. A total of 36 subjects were enrolled into 3 successive cohorts (A, B, C with 12 subjects per cohort) and randomized in a 3:1 ratio to receive treatment with ALZ-801 capsules (9 subjects) or placebo capsules (3 subjects) for 2 weeks. Progression to the next cohort was permitted after review of safety and available PK data suggested that it was safe to do so. Subjects were confined to the clinical unit for the first day of dosing (Day 1 and for Days 7 through 14). Subjects took investigational drug at home for Days 2 through 6).
Cohorts A was dosed in the fasted state and evaluated 171 mg ALZ-801 or placebo QD for 1 day, followed by 171 mg ALZ-801 or placebo BID for 6 days and 256.5 mg or placebo QD for 7 days.
Cohort B was dosed in the fasted state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days and 340 mg or placebo QD for 7 days.
Cohort C was dosed in the fed state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days, then 340 mg or placebo BID for 6 days and 340 mg or placebo QD for 1 day.
Part 2 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of multiple doses of prototype ALZ-801 tablet formulation in healthy elderly subjects.
Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female subjects aged 60 to 75 years, inclusive. A total of 12 subjects were enrolled into one cohort (D) and randomized in a 3:1 ratio to receive treatment with ALZ-801 tablets (9 subjects) or placebo capsules (3 subjects) for 1 week.
Cohort D was dosed in the fed state and evaluated 265 mg ALZ-801 or placebo QD for 1 day, followed by 265 mg ALZ-801 prototype tablet or placebo BID for 5 days, 265 mg or placebo QD for 1 day.
For all subjects in the study blood and urine samples for the determination of concentrations of ALZ-801, and its metabolites, were collected for up to 24 h after the first dose of medication on Day1; and for up to 48 hours after the last dose of medication on Day 7 (Cohort D) or Day 14 (Cohorts A, B and C). All subjects had blood samples and safety assessment at 72 and 96 hours after the final dose of medication. All subjects returned for a post treatment follow-up 7-10 days after the last dose of study medication.
- Conditions
- Alzheimer Disease
- Being tested
- ALZ-801 or matching placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALZ-801 or matching placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort A Capsule - Fasted | Experimental | ALZ-801 171 mg or matching placebo once daily Day 1, ALZ-801 171 mg or matching placebo twice daily Days 2-7, ALZ-801 256.5 mg or matching placebo once daily Days 8-14 Receives: Drug: ALZ-801 or matching placebo |
| Cohort B Capsule - Fasted | Experimental | ALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 or matching placebo mg twice daily Days 2-7, ALZ-801 340 mg or matching placebo once daily Days 8-14 Receives: Drug: ALZ-801 or matching placebo |
| Cohort C Capsule - Fed | Experimental | ALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 mg or matching placebo twice daily Days 2-7, ALZ-801 340 mg or matching placebo twice daily Days 8-13, ALZ-801 340 mg or matching placebo once daily Day 14 Receives: Drug: ALZ-801 or matching placebo |
| Cohort D Tablet - Fed | Experimental | ALZ-801 265 mg or matching placebo once daily Day 1, ALZ-801 265 mg or matching placebo twice daily Days 2-6, ALZ-801 265 mg or matching placebo once daily Day 7 Receives: Drug: ALZ-801 or matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as a measure of safety and tolerability
Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Assessments reported as AEs or SAEs include physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
Measured: Duration of dosing: 14 days for Part 1; 7 days for Part 2
Cmax for ALZ-801 and tramiprosate
Maximum concentration after dosing [Cmax] measured as ng/ml
Measured: Days 1, 7 and 14
Tmax for ALZ-801 and tramiprosate
Time to reach Cmax [Tmax] measured in hours (h) after dosing
Measured: Days 1, 7 and 14
AUC for ALZ-801 and tramiprosate
AUC from time zero to time t (AUCt)
Measured: Days 1, 7 and 14
t1/2 for ALZ-801 and tramiprosate
Elimination half-life (t1/2) measured in hours after dosing
Measured: Days 1, 7, 14
Renal clearance of ALZ-801 and tramiprosate
Clearance (CLr) measured in mL/min
Measured: Days 1, 7 and 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start26 Sep 2015
- Primary completion4 Jul 2016
- Study completion4 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Sequential
- Model description
- double blind, placebo controlled, matching placebo
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alzheon Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quotient Clinical
- Responsible party
- Sponsor
- Investigators
- Pui Leung, MD, Principal investigator, Quotient Clinical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157712
- Sponsor's protocol ID
- ALZ-801-103
- Status last verified
- Nov 2019
- First submitted
- 4 Nov 2019
- Last updated
- 19 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hey JA, Yu JY, Versavel M, Abushakra S, Kocis P, Power A, Kaplan PL, Amedio J, Tolar M. Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. Clin Pharmacokinet. 2018 Mar;57(3):315-333. doi: 10.1007/s40262-017-0608-3.
PubMed 29063518
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single Centre, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics in Plasma and Urine of Multiple Ascending Doses of ALZ-801 in Healthy Elderly Subjects
- ClinicalTrials.gov ID
- NCT04157712
- Acronym / sponsor ID
- ALZ-801-103
- Conditions
- Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Alzheon Inc.Industry (pharma, biotech, devices)
- Collaborators
- Quotient Clinical
- Study start
- 26 Sep 2015 (actual)
- Primary completion
- 4 Jul 2016 (actual)
- Study completion
- 4 Jul 2016 (actual)
- First posted
- 8 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I, single-center, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability, and pharmacokinetics (PK) in plasma and urine, of multiple ascending doses of ALZ-801 (capsule, Part 1; prototype tablet Part 2) and the primary metabolite in healthy male or female subjects.
Detailed description
The study was conducted in two parts:
Part 1 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of multiple doses of ALZ-801 capsule formulation in healthy elderly subjects.
Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female subjects aged 50 to 75 years, inclusive. A total of 36 subjects were enrolled into 3 successive cohorts (A, B, C with 12 subjects per cohort) and randomized in a 3:1 ratio to receive treatment with ALZ-801 capsules (9 subjects) or placebo capsules (3 subjects) for 2 weeks. Progression to the next cohort was permitted after review of safety and available PK data suggested that it was safe to do so. Subjects were confined to the clinical unit for the first day of dosing (Day 1 and for Days 7 through 14). Subjects took investigational drug at home for Days 2 through 6).
Cohorts A was dosed in the fasted state and evaluated 171 mg ALZ-801 or placebo QD for 1 day, followed by 171 mg ALZ-801 or placebo BID for 6 days and 256.5 mg or placebo QD for 7 days.
Cohort B was dosed in the fasted state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days and 340 mg or placebo QD for 7 days.
Cohort C was dosed in the fed state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days, then 340 mg or placebo BID for 6 days and 340 mg or placebo QD for 1 day.
Part 2 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of multiple doses of prototype ALZ-801 tablet formulation in healthy elderly subjects.
Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female subjects aged 60 to 75 years, inclusive. A total of 12 subjects were enrolled into one cohort (D) and randomized in a 3:1 ratio to receive treatment with ALZ-801 tablets (9 subjects) or placebo capsules (3 subjects) for 1 week.
Cohort D was dosed in the fed state and evaluated 265 mg ALZ-801 or placebo QD for 1 day, followed by 265 mg ALZ-801 prototype tablet or placebo BID for 5 days, 265 mg or placebo QD for 1 day.
For all subjects in the study blood and urine samples for the determination of concentrations of ALZ-801, and its metabolites, were collected for up to 24 h after the first dose of medication on Day1; and for up to 48 hours after the last dose of medication on Day 7 (Cohort D) or Day 14 (Cohorts A, B and C). All subjects had blood samples and safety assessment at 72 and 96 hours after the final dose of medication. All subjects returned for a post treatment follow-up 7-10 days after the last dose of study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- double blind, placebo controlled, matching placebo
| Arm | Type | Receives |
|---|---|---|
| Cohort A Capsule - Fasted | Experimental | Drug: ALZ-801 or matching placeboALZ-801 171 mg or matching placebo once daily Day 1, ALZ-801 171 mg or matching placebo twice daily Days 2-7, ALZ-801 256.5 mg or matching placebo once daily Days 8-14 |
| Cohort B Capsule - Fasted | Experimental | Drug: ALZ-801 or matching placeboALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 or matching placebo mg twice daily Days 2-7, ALZ-801 340 mg or matching placebo once daily Days 8-14 |
| Cohort C Capsule - Fed | Experimental | Drug: ALZ-801 or matching placeboALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 mg or matching placebo twice daily Days 2-7, ALZ-801 340 mg or matching placebo twice daily Days 8-13, ALZ-801 340 mg or matching placebo once daily Day 14 |
| Cohort D Tablet - Fed | Experimental | Drug: ALZ-801 or matching placeboALZ-801 265 mg or matching placebo once daily Day 1, ALZ-801 265 mg or matching placebo twice daily Days 2-6, ALZ-801 265 mg or matching placebo once daily Day 7 |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy males, and females
- Age: 50-75 years, Part 1; 60-75 years Part 2
- Females must be of non-childbearing potential
- Body Mass Index 18-35 kg/m squared;
- Vital signs normal for age: BP 90-160/40-90 mmHg; HR 50 to 90 bpm)
Key exclusion criteria (6 listed)
- Body weight < 50 kg
- History of any drug or alcohol abuse in the past 2 years
- Subjects known to have a creatinine clearance of <60 mL/min
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- History of clinically significant cardiovascular, pulmonary, chronic respiratory, renal, hepatic, GI, immunologic, endocrine, neurologic, psychiatric or thromboembolic disease
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 |
|---|---|---|
| ALZ-801 or matching placebo | Drug | Cohort A Capsule - Fasted, Cohort B Capsule - Fasted, Cohort C Capsule - Fed, Cohort D Tablet - Fed |
Primary outcome
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Duration of dosing: 14 days for Part 1; 7 days for Part 2
Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Assessments reported as AEs or SAEs include physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
Cmax for ALZ-801 and tramiprosate
Time frame: Days 1, 7 and 14
Maximum concentration after dosing [Cmax] measured as ng/ml
Tmax for ALZ-801 and tramiprosate
Time frame: Days 1, 7 and 14
Time to reach Cmax [Tmax] measured in hours (h) after dosing
AUC for ALZ-801 and tramiprosate
Time frame: Days 1, 7 and 14
AUC from time zero to time t (AUCt)
t1/2 for ALZ-801 and tramiprosate
Time frame: Days 1, 7, 14
Elimination half-life (t1/2) measured in hours after dosing
Renal clearance of ALZ-801 and tramiprosate
Time frame: Days 1, 7 and 14
Clearance (CLr) measured in mL/min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
- Results publication: PubMed 29063518Hey JA, Yu JY, Versavel M, Abushakra S, Kocis P, Power A, Kaplan PL, Amedio J, Tolar M. Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. Clin Pharmacokinet. 2018 Mar;57(3):315-333. doi: 10.1007/s40262-017-0608-3.
- Individual participant dataSharing planned: No
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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.
Pui Leung, MD principal investigator
Quotient Clinical
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 of Alzheimer Disease, run by Alzheon Inc. at 1 site in United Kingdom.
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 6 inclusion and 6 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: finished, as of the sponsor's last update on 19 Nov 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 Kingdom. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of participants with adverse events as a measure of safety and tolerability (time frame: Duration of dosing: 14 days for Part 1; 7 days for Part 2). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04157712, which also lists 1 linked publication.
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 19 Nov 2019.