LYT-300 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT05129865
• Recruitment Status: Completed
• First Posted: November 22, 2021
• Last Update Posted: November 13, 2023
• Sponsor: PureTech
• Collaborator: Novotech (Australia) Pty Limited
• Information provided by (Responsible Party): PureTech

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: LYT-300; Other: Placebo	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Investigator)

Masking Description

Parts 1, 2 and 3 are double blind during the data collection. Determination for dose escalation may be made under unblinded conditions by assessors.

Part 4 consists of 2 groups. Group 1 (the validation group) will be single-arm placebo. Group 2 (the test group) will be double blind during data collection.

• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 7, 2021
• Actual Primary Completion Date: October 18, 2023
• Actual Study Completion Date: October 23, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Main Inclusion Criteria:

Parts 1, 2, 3 and 4: Healthy Volunteers

1. Male or female between 18 and 55 years old (inclusive) at the time of screening.
2. 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

1. Evidence or history of any condition or situation that adversely impacts a normal sleep-wake cycle.
2. Confirmed COVID-19 infection within 2 months of screening, known exposure to another person with COVID-19 within 14 days of screening
3. History of illness with fever within 28 days prior to the first dose.
4. A history of, or current evidence for, serious mental illness

Contacts and Locations

Locations

Australia, South Australia

CMAX

Adelaide, South Australia, Australia, 5000

Sponsors and Collaborators

PureTech

Novotech (Australia) Pty Limited

More Information

• Responsible Party: PureTech
• ClinicalTrials.gov Identifier: NCT05129865
• Other Study ID Numbers: LYT-300-2021-101
• First Posted: November 22, 2021
• Last Update Posted: November 13, 2023
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No