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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03668314
• Other study ID #: RDN-929-101
• Status: Completed
• Phase: Phase 1
• Start date: October 10, 2018
• Est. completion date: April 15, 2019

Study information

• Verified date: February 2020
• Source: Alkermes, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: April 15, 2019
• Est. primary completion date: April 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• RDN-929
Single dose from 2 mg to TBD
• Placebo oral capsule
Matching placebo Single dose
• RDN-929 TBD dose
Fed vs fast dose TBD based upon results of previous cohorts
• RDN-929
Multiple dose based on results of previous cohorts
• Placebo oral capsule
Matching placebo multiple dose

Locations

Country	Name	City	State
Netherlands	QPS Netherlands B.V.	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
Alkermes, Inc.	QPS Netherlands B.V.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events	Listing and summary of AE incidence	Screening to end of study, up to 7 weeks
Primary	Number of subjects with Physical exam findings	Listing of clinically significant changes in PE findings	Screening to end of study, up to 7 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	Number of subjects with C-SSRS changes	Listing of results	Baseline to end of study (Part 3 only), up to 7 weeks
Primary	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	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)
Secondary	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)
Secondary	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)