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

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single and Multiple Doses of Orally Administered RDN-929 in Healthy Adult and Elderly Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: RDN-929; Drug: RDN-929; Drug: Placebo oral capsule; Drug: Placebo oral capsule; Drug: RDN-929 TBD dose

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 Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • QPS Netherlands B.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1:1 - 1:6 RDN-929; RDN-929 single dose capsule	Drug: RDN-929; Single dose from 2 mg to TBD; Drug: RDN-929; Multiple dose based on results of previous cohorts
Placebo Comparator: Cohort 1:1 - 1:6 placebo; Placebo single dose capsule	Drug: Placebo oral capsule; Matching placebo Single dose; Drug: Placebo oral capsule; Matching placebo multiple dose
Experimental: Cohort 2:1; Fed/Fast RDN-929	Drug: RDN-929 TBD dose; Fed vs fast dose TBD based upon results of previous cohorts
Experimental: Cohort 3:1- 3:4 RDN-929; RDN-929 multiple dose capsules once daily for 12 days	Drug: RDN-929; Single dose from 2 mg to TBD; Drug: RDN-929; Multiple dose based on results of previous cohorts
Placebo Comparator: Cohort 3:1- 3:4 placebo; placebo multiple dose capsules once daily for 10 days	Drug: Placebo oral capsule; Matching placebo Single dose; Drug: Placebo oral capsule; Matching placebo multiple dose

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Alkermes, Inc.
• Collaborators: QPS Netherlands B.V.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2018
• Primary Completion (Actual): April 15, 2019
• Study Completion (Actual): April 15, 2019

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: RDN-929-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No