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

Sponsor
Alkermes, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03668314
Collaborator
QPS Netherlands B.V. (Industry)
84
Enrollment
1
Location
5
Arms
6.1
Actual Duration (Months)
13.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Parts 1 and 3 are parallel designs with escalating doses within each part. Part 2 is a FE cross-over studyParts 1 and 3 are parallel designs with escalating doses within each part. Part 2 is a FE cross-over study
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
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
Actual Study Start Date :
Oct 10, 2018
Actual Primary Completion Date :
Apr 15, 2019
Actual Study Completion Date :
Apr 15, 2019

Arms and Interventions

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
Placebo Comparator: Cohort 1:1 - 1:6 placebo

Placebo single dose capsule

Drug: Placebo oral capsule
Matching placebo Single 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
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 multiple dose

Outcome Measures

Primary Outcome Measures

  1. Number of subjects with adverse events [Screening to end of study, up to 7 weeks]

    Listing and summary of AE incidence

  2. Number of subjects with Physical exam findings [Screening to end of study, up to 7 weeks]

    Listing of clinically significant changes in PE findings

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Number of subjects with C-SSRS changes [Baseline to end of study (Part 3 only), up to 7 weeks]

    Listing of results

  9. 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

  1. 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

  2. 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

  3. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 QPS Netherlands B.V. Groningen Netherlands

Sponsors and Collaborators

  • Alkermes, Inc.
  • QPS Netherlands B.V.

Investigators

  • Principal Investigator: PI, QPS

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alkermes, Inc.
ClinicalTrials.gov Identifier:
NCT03668314
Other Study ID Numbers:
  • RDN-929-101
First Posted:
Sep 12, 2018
Last Update Posted:
Feb 20, 2020
Last Verified:
Feb 1, 2020
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No

Study Results

No Results Posted as of Feb 20, 2020