Department of Defense PTSD Adaptive Platform Trial Intervention A - Fluoxetine

A Phase 2, Multi-center, Multi-arm, Randomized, Placebo-controlled, Double-blind, Adaptive Platform Study to Evaluate the Safety, Tolerability, and Efficacy of Potential Pharmacotherapeutic Interventions in Active-Duty Service Members and Veterans With PTSD

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design.

Intervention A - Fluoxetine will assess the safety and efficacy of fluoxetine in participants with PTSD.

Please see NCT05422612 for information on the S-21-02 Master Protocol.

Study Overview

• Status: Recruiting
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Drug: Intervention A Placebo; Drug: Intervention A Fluoxetine Hydrochloride (HCl)

Detailed Description

The general structure of this Adaptive Platform Trial (APT) consists of a 30-day Screening Period, a 12-week Platform Treatment Period, and a 4-week Safety Follow-up. The S-21-02 Platform Trial will evaluate the safety and efficacy of multiple investigational products for the treatment of PTSD (see NCT05422612 for Master Protocol information). Participants are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control subjects, where all interventions may be compared to a common control (placebo). This record only includes information relevant to the fluoxetine cohort.

Once a participant meets all eligibility criteria for the Master Protocol, eligibility for each currently enrolling intervention cohort is assessed. Eligible participants will be randomized with equal probability into a cohort. Participants randomized to the fluoxetine cohort are then randomly assigned to receive either fluoxetine or placebo in a ratio defined by the number of cohorts for which they are eligible, for the duration of the 12-week treatment period.

Parties interested in having their intervention considered for testing within the DOD PTSD APT should complete a request for information form using this webpage https://citeline.qualtrics.com/jfe/form/SV_0oDoJXvIL7EFM1M.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr. Kimberly del Carmen; Phone Number: Please reach out by email; Email: kimberly.a.delcarmen.civ@health.mil

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Advanced Discovery Research
      • Contact: Advanced Discovery Research Contact; Phone Number: 470-777-8839; Email: contact@advdiscovery.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT05422612).

Exclusion Criteria:

The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT05422612).

1. Recent history of treatment for PTSD with fluoxetine at doses of 20 mg daily, for at least 4 weeks. A remote history of treatment with fluoxetine for non-PTSD symptoms will be discussed on a case-by-case basis with the contract research organization (CRO) Medical Monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention A: Fluoxetine HCl	Drug: Intervention A Fluoxetine Hydrochloride (HCl); Fluoxetine will be administered at 10 to 60 mg daily. The initial dose for all participants will be 10 mg daily for 1 week, then increased to 20 mg daily for 2 weeks, then increased to 40 mg daily for 2 weeks, then increased to 60 mg daily for the remainder of the trial. One reduction in dose due to tolerability will be allowed. When a participant's dose is decreased due to tolerability, the dose will not be increased.
Placebo Comparator: Intervention A Placebo	Drug: Intervention A Placebo; A matching placebo will be administered at 10 to 60 mg daily in the same regimen as the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of new or worsening suicidal thoughts or behaviors as measured by change in Columbia Suicide Severity Rating Scale (C-SSRS) score from baseline.	The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). This 5-item subscale ranges from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent).	12 Weeks
Absolute change in the Clinician-Administered PTSD Scale-5-Revised (CAPS-5-R) Past Month total score at Week 12 (Final/Early termination Visit).	A change in PTSD symptom severity from baseline as measured by CAPS-5-R Past Month. The range of the scale is 0-200. The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of treatment-emergent adverse events (TEAEs).	The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.	12 Weeks
Severity of treatment-emergent adverse events (TEAEs).	The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.	12 Weeks
Severity of serious adverse events (SAEs).	The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.	12 Weeks
Frequency of serious adverse events (SAEs).	The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA.	12 Weeks
Relative change from Baseline to Week 12 in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score.	A relative change in PTSD symptom severity from baseline as measured by CAPS-5-R Past Month. The range of the scale is 0-200. The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.	12 Weeks
Number of participants with a Response Rate ≥30%	≥30% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.	12 Weeks
Number of participants with a Response Rate ≥50%	≥50% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome.	12 Weeks
Number of participants Achieving Remission	Achieving remission: defined as the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score <18. The range of the scale is 0-200. The higher the score, the worse the PTSD severity.	12 Weeks

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: PPD; Idorsia Pharmaceuticals Ltd.; Berry Consultants; Cambridge Cognition Ltd; Citeline

Publications and helpful links

General Publications

• Viele K. Allocation in platform trials to maintain comparability across time and eligibility. Stat Med. 2023 Jul 20;42(16):2811-2818. doi: 10.1002/sim.9750. Epub 2023 Apr 23.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Selective Serotonin Reuptake Inhibitors; Fluoxetine
• Other Study ID Numbers: S-21-02 (Fluoxetine)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No