LYT-300 in Healthy Volunteers

Study Overview
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Brief Summary
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Part 1 is a single ascending dose (SAD) trial in healthy volunteers (HV) to assess the safety, tolerability, and pharmacokinetic (PK) profile of orally administered LYT-300. Part 2 is a crossover assessment in HV of the effects of food on the safety, tolerability, and PK profile of orally administered LYT-300. Part 3 is a multiple ascending dose (MAD) trial in HV to assess the safety, tolerability, and PK profile of multiple doses (up to 7 days) of orally administered LYT-300. Part 4 is an assessment of the effects of LYT-300 vs. placebo on pharmacodynamic and patient reported outcome response to a validated clinical model of anxiety.

Detailed Description
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Part 1: This is a randomized, double-blind, placebo-controlled, SAD design to assess the safety, tolerability, and PK profile of orally administered LYT-300 in HV, in a 3-period, 3-sequence, crossover, dose escalation design. Part 2: This is a randomized, open label, 3-period, 3-sequence, crossover assessment of the effects of food on the PK, safety, and tolerability of orally administered LYT-300 in HV. A single dose of LYT-300 will be administered on 3 occasions, separated by a minimum 7-day washout period. Part 2 is planned as a single dosing cohort. Part 3: This is a randomized, double-blind, placebo-controlled, sequential, MAD trial in HV to assess the safety, tolerability, and PK profile of multiple doses (up to 7 days) of orally administered LYT-300. This part will include ascending doses given either once daily in the morning (QAM), once daily in the evening (QHS), or twice daily (BID). Part 4: This is a double-blind, randomized assessment of the effects in HV of a single dose of LYT-300 vs. placebo on pharmacodynamic and patient reported outcome response to a validated clinical model of anxiety.

Official Title
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A Phase 1, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LYT-300 in Healthy Volunteers, and a Phase 1b/2a Study Part to Assess Effects of a Single Dose of LYT-300 vs. Placebo on the Response to a Standardized Behavioural Challenge in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LYT-300
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Parts 1, 2, 3 and 4: Healthy Volunteers Male or female between 18 and 55 years old (inclusive) at the time of screening. In good general health at screening, free from clinically significant unstable medical, surgical or psychiatric illness, at the discretion of the Investigator. Main Exclusion Criteria: Parts 1, 2, 3 and 4: Healthy Volunteers Evidence or history of any condition or situation that adversely impacts a normal sleep-wake cycle. Confirmed COVID-19 infection within 2 months of screening, known exposure to another person with COVID-19 within 14 days of screening History of illness with fever within 28 days prior to the first dose. A history of, or current evidence for, serious mental illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 consists of 1 Arm with crossover of active treatment and placebo; Part 2 consists of 1 Arm with active treatment; Part 3 consists of 4 Arms with active treatment or placebo; Part 4 consists of 2 arms with active or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYT-300 in healthy volunteers LYT-300, Doses TBD<br>Subjects will crossover across 3 dosing periods in which they will receive placebo and two experimental dose levels | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>Other: Placebo<br>* Placebo for LYT-300<br>|
| Experimental: LYT-300 in healthy volunteers LYT-300<br>LYT-300, Dose TBD with and without food, separated by 7-day washout | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>|
| Experimental: LYT-300, Dose TBD QAM every 24 h for 7 days<br> | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>|
| Placebo Comparator: Placebo QAM every 24 h for 7 days<br> | Other: Placebo<br>* Placebo for LYT-300<br>|
| Placebo Comparator: Placebo QHS every 24 h for 7 days<br> | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>Other: Placebo<br>* Placebo for LYT-300<br>|
| Experimental: LYT-300 in healthy volunteers LYT-300, Dose TBD QHS every 24 h for 7 days<br> | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>Other: Placebo<br>* Placebo for LYT-300<br>|
| Experimental: LYT-300<br> | Drug: LYT-300<br>* A prodrug of allopregnanolone, a small molecule drug<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo for LYT-300<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: treatment-emergent adverse events [TEAEs] | Evaluate the safety and tolerability in healthy volunteers following single or multiple oral doses of LYT-300 as measured by TEAEs. | 7 days (main time frame) | 
| Effect of food in healthy volunteers | Measure concentration of allopregnanolone in blood plasma in fed or fasted subjects administered a single dose of LYT-300 | 2 days (main time frame) | 
| Salivary cortisol | Change in salivary cortisol | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use pharmacokinetics to characterize the blood plasma concentration of allopregnanolone after administration of LYT-300 | Measure the blood plasma concentrations of allopregnanolone in healthy volunteers after single and multiple doses of LYT-300 administered up to 7 days | 7 days (main time frame) |