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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: RDN-929
* Drug: Placebo oral capsule
* Drug: RDN-929 TBD dose
* Drug: RDN-929
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parts 1 and 3 are parallel designs with escalating doses within each part. Part 2 is a FE cross-over study
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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) |