Single and Multiple Ascending Dose and Food Effect PK Study in Healthy Adult and Elderly Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo oral capsule; Drug: RDN-929 TBD dose; Drug: RDN-929

• Registration Number: NCT03668314
• Lead Sponsor: Alkermes, Inc.

Brief Summary

A three (3) part study to evaluate the safety, tolerability and PK of RDN-929

Detailed Description

Part 1 (Randomized, Double Blind):

Up to 6 single ascending doses of RDN-929 are planned to be tested in 6 cohorts of 8 healthy males (Cohort 1:1 to 1:6). Within each cohort subjects will be randomly assigned to receive either a single dose of RDN-929 (6 subjects) or matched placebo (2 subjects).

Part 2 (Open):

Part 2 will consist of 2 crossover treatment periods in one cohort of 12 healthy elderly subjects (at least 3 of each gender), aged 55-80 years. The treatments will be separated by a washout period of at least 7 days. The dose selected for this part of the study will be based on the results of Part 1.

In Period 1, subjects will be randomized to receive a single dose of RDN-929 in either fasted or fed status. In Period 2, subjects will receive a single dose of RDN-929 under the alternate status.

Part 3 (Randomized, Double Blind):

Multiple ascending doses (MAD) of RDN-929 are planned to be tested in up to 4 cohorts of 8 healthy elderly subjects (at least 3 of each gender per dose level cohort), aged 55-80 years. The doses will be selected by the safety review committee (SRC) based on all available safety, tolerability and PK data and after approval by the ethics committee.

Within each cohort subjects will be randomly assigned to receive either, RDN-929 once daily (6 subjects) or matched placebo (2 subjects) once daily for 12 days. Escalation to the next higher dose level will be based upon a review of the safety and tolerability data.

Study Timeline

• Study First Submitted: 2018-09-06
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-12
• Study Start: 2018-10-10
• Primary Completion: 2019-04-15
• Study Completion: 2019-04-15
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-19
• Last Update Posted: 2020-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

• Healthy as determined by the Investigator, based on a medical evaluation including medical history physical examination, neurological examination, laboratory tests and cardiac monitoring
• Men, age 18-54 years inclusive at Screening (Part 1) or men and postmenopausal or surgically sterile women age 55-80

Exclusion Criteria

• Any history of major psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
• Acute suicidality or history of suicidal behavior.
• Alanine aminotransferase or aspartate aminotransferase levels greater than 1.5 times the upper limit of normal (ULN) at Screening. One retest is allowed.
• A corrected QT interval measurement corrected according to the Fridericia rule (QTcF) > 450 msec during controlled rest at screening or between screening and first dose administration, or family history of long QT syndrome.
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the Investigator or Medical Monitor, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
• A clinically significant vital signs abnormality at screening or between screening and first dose administration. This includes, but is not limited to, the following, in the supine position: (a) systolic blood pressure < 90 or >150 mmHg, (b) diastolic blood pressure <50 or > 95 mmHg, or (c) heart rate < 45 or >100 beats per minute.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3:1- 3:4 placebo	Placebo oral capsule	placebo multiple dose capsules once daily for 10 days
Cohort 1:1 - 1:6 placebo	Placebo oral capsule	Placebo single dose capsule
Cohort 2:1	RDN-929 TBD dose	Fed/Fast RDN-929
Cohort 1:1 - 1:6 RDN-929	RDN-929	RDN-929 single dose capsule
Cohort 3:1- 3:4 RDN-929	RDN-929	RDN-929 multiple dose capsules once daily for 12 days

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events	Screening to end of study, up to 7 weeks	Listing and summary of AE incidence
Number of subjects with Physical exam findings	Screening to end of study, up to 7 weeks	Listing of clinically significant changes in PE findings
Number of subjects with Clinical safety lab changes	Screening to end of study, up to 7 weeks	Listing and change from baseline to end of study
Number of subjects with Systolic blood pressure changes	Screening to end of study, up to 7 weeks	Listing and change from baseline to end of study
Number of subjects with Heart rate changes	Screening to end of study, up to 7 weeks	Listing and change from baseline to end of study
Number of subjects with 12 Lead ECG changes	Screening to end of study, up to 7 weeks	Change in 12-lead ECG parameters from baseline to end of study
Number of subjects with 3 Lead ECG findings	Predose to 8 hours post dose on Day 1 (Parts 1 and 2) and Days 1 and 12 (Part 3)	Listing of findings
Number of subjects with C-SSRS changes	Baseline to end of study (Part 3 only), up to 7 weeks	Listing of results
Number of subjects with Visual analogue scale changes	Baseline to end of study for Part 1 and 3, up to 7 weeks	VAS for headache and nausea

Secondary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration, Cmax	Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)	Of RDN-929 and primary metabolite
Time to reach maximum observed plasma concentration, Tmax	Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)	Of RDN-929 and primary metabolite
Area Under the plasma concentration time curve, AUC	Predose to 48 hours post last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)	Of RDN-929 and primary metabolite

Trial Locations

Locations (1)

QPS Netherlands B.V.; 🇳🇱 Groningen, Netherlands