Clinical trial NCT03668314: Single and Multiple Ascending Dose and Food Effect PK Study in Healthy Adult and Elderly Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Alkermes, Inc.
Sponsor class: INDUSTRY
Collaborators: name: QPS Netherlands B.V.
First posted: 2018-09-12
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parts 1 and 3 are parallel designs with escalating doses within each part. Part 2 is a FE cross-over study
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with Physical exam findings
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with Clinical safety lab changes
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with Systolic blood pressure changes
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with Heart rate changes
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with 12 Lead ECG changes
timeFrame: Screening to end of study, up to 7 weeks
measure: Number of subjects with 3 Lead ECG findings
timeFrame: Predose to 8 hours post dose on Day 1 (Parts 1 and 2) and Days 1 and 12 (Part 3)
measure: Number of subjects with C-SSRS changes
timeFrame: Baseline to end of study (Part 3 only), up to 7 weeks
measure: Number of subjects with Visual analogue scale changes
timeFrame: Baseline to end of study for Part 1 and 3, up to 7 weeks
Secondary outcomes:
measure: Maximum observed plasma concentration, Cmax
timeFrame: Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)
measure: Time to reach maximum observed plasma concentration, Tmax
timeFrame: Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)
measure: Area Under the plasma concentration time curve, AUC
timeFrame: Predose to 48 hours post last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: QPS Netherlands B.V.
Study officials:
affiliation: QPS Holdings LLC
name: PI
role: PRINCIPAL_INVESTIGATOR
References: