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

Tracking Information

• First Submitted Date: October 31, 2021
• First Posted Date: November 22, 2021
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: December 7, 2021
• Actual Primary Completion Date: October 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2023)

• 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.
• 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
• Salivary cortisol [ Time Frame: 60 minutes ]
  Change in salivary cortisol

Original Primary Outcome Measures (submitted: November 11, 2021)

• 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.
• 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

Current Secondary Outcome Measures (submitted: November 11, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: LYT-300 in Healthy Volunteers
• 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

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.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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

• Condition: Healthy Volunteers

Intervention

• Drug: LYT-300
  A prodrug of allopregnanolone, a small molecule drug
• Other: Placebo
  Placebo for LYT-300

Study Arms

• 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
  Interventions:

  • Drug: LYT-300
  • Other: Placebo
• Experimental: LYT-300 in healthy volunteers LYT-300
  LYT-300, Dose TBD with and without food, separated by 7-day washout
  Intervention: Drug: LYT-300
• Experimental: LYT-300, Dose TBD QAM every 24 h for 7 days
  Intervention: Drug: LYT-300
• Placebo Comparator: Placebo QAM every 24 h for 7 days
  Intervention: Other: Placebo
• Placebo Comparator: Placebo QHS every 24 h for 7 days
  Interventions:

  • Drug: LYT-300
  • Other: Placebo
• Experimental: LYT-300 in healthy volunteers LYT-300, Dose TBD QHS every 24 h for 7 days
  Interventions:

  • Drug: LYT-300
  • Other: Placebo
• Experimental: LYT-300
  Intervention: Drug: LYT-300
• Placebo Comparator: Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2023): 186
• Original Estimated Enrollment (submitted: November 11, 2021): 90
• Actual Study Completion Date: October 23, 2023
• Actual Primary Completion Date: October 18, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT05129865
• Other Study ID Numbers: LYT-300-2021-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: PureTech
• Original Responsible Party: Same as current
• Current Study Sponsor: PureTech
• Original Study Sponsor: Same as current
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Not Provided
• PRS Account: PureTech
• Verification Date: November 2022