Multiple Ascending Dose Study of ALZ-801

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: ALZ-801 or matching placebo

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A Capsule - Fasted; 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	Drug: ALZ-801 or matching placebo
Experimental: Cohort B Capsule - Fasted; 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	Drug: ALZ-801 or matching placebo
Experimental: Cohort C Capsule - Fed; 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	Drug: ALZ-801 or matching placebo
Experimental: Cohort D Tablet - Fed; 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	Drug: ALZ-801 or matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Days 1, 7 and 14
Tmax for ALZ-801 and tramiprosate	Time to reach Cmax [Tmax] measured in hours (h) after dosing	Days 1, 7 and 14
AUC for ALZ-801 and tramiprosate	AUC from time zero to time t (AUCt)	Days 1, 7 and 14
t1/2 for ALZ-801 and tramiprosate	Elimination half-life (t1/2) measured in hours after dosing	Days 1, 7, 14
Renal clearance of ALZ-801 and tramiprosate	Clearance (CLr) measured in mL/min	Days 1, 7 and 14

Collaborators and Investigators

• Sponsor: Alzheon Inc.
• Collaborators: Quotient Clinical
• Investigators: Principal Investigator: Pui Leung, MD, Quotient Clinical

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2015
• Primary Completion (Actual): July 4, 2016
• Study Completion (Actual): July 4, 2016

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: ALZ-801-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No