A Study of Diclofenac Gel in Women With Primary Dysmenorrhea (DARE-PDM1)

A Phase 1, Multi-site, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Pharmacokinetics, Safety and Preliminary Efficacy of Two Strengths of DARE-PDM1 (1% or 3%) Versus Placebo Among Women With Symptomatic Primary Dysmenorrhea

The goal of this clinical trial is to compare 1% and 3% diclofenac gel (DARE-PDM1) to placebo in women with symptomatic primary dysmenorrhea. The main question it aims to answer are:

Is DARE-PDM1 1%, 3% diclofenac gel systemically safe? What are the systemic levels of DARE-PDM1 1%, 3% diclofenac gel in plasma and vaginal fluid following 1 dose and 3 doses.

Participants will be seen for routine safety evaluations and complete a daily diary recording dysmenorrhea associated pain.

Study Overview

• Status: Active, not recruiting
• Conditions: Dysmenorrhea Primary
• Intervention / Treatment: Drug: Diclofenac 1%; Drug: Diclofenac 3%; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: VP Clinical Operations; Phone Number: 856-926-7655; Email: jhatheway@darebioscience.com
• Study Contact Backup: Name: Medical Director; Phone Number: 856-926-7655; Email: athurman@darebioscience.com

Study Locations

• Australia
  • Western Australia
    • Adelaide, Western Australia, Australia
      • PARC Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females ages 18- 50 years old (inclusive)
• Self-assessment of historic dysmenorrhea associated pain level of ≥ 5 on a scale of 0 - 10 in at least one of the following anatomic sites: pelvic/vaginal pain, low back pain, while not using NSAIDs or hormonal contraception.
• Non-pregnant status
• If applicable, agrees to be sexually abstinent and place nothing in the vagina during the 120 hours between visits 3 and 8 and the 3-day period of the multiple dose regimen.
• Agrees to use adequate non-hormonal birth control during the trial (e.g. study provided male condoms without nonoxynol-9 lubricant, tubal sterilization, heterosexual abstinence) (Because hormonal birth control is a known off label treatment for dysmenorrhea, if the participant is on hormonal birth control other than Depo-Provera contraceptive injection, she agrees to discontinue it and have at least one spontaneous intervening menses before the start of the study period. If using Depo Provera, has not had an injection within the 4 months before Visit 1 and must have had a spontaneous menses prior to visit 2.)
• Provides informed consent for participating in the trial
• Willingness to use only study-provided oral paracetamol as rescue pain medication for dysmenorrhea, if needed according to investigator's instruction.
• Patient is fluent in the English language.
• Patient is capable of understanding and complying with the protocol and agrees to sign the informed consent document.
• Patient has had a cervical screen performed within five years prior to Visit 1 and can provide documentation indicating normal test results consistent with Australian Health guidelines. If the patient cannot provide documentation, a cervical screen will be performed at Visit 1. Patients with abnormal findings will be excluded from study participation and be referred for follow-up medical care as appropriate.

Exclusion Criteria:

• Positive pregnancy test
• Unwilling or unable to comply with protocol
• Allergic to diclofenac or other non-steroidal anti-inflammatory drugs (NSAIDs)
• Patients with severe liver, kidney or heart failure
• After the use of aspirin or other nonsteroidal anti-inflammatory drugs, asthma, nasal polyps, angioedema and urticaria have occurred in the past
• Current active peptic ulcer bleeding or perforation
• Have a history of significant upper gastrointestinal disease
• Have a chronic pain syndrome other than dysmenorrhea which could confound preliminary efficacy data (e.g., chronic low back pain unrelated to menses)
• Have a positive Sexually Transmitted Infection (STI) test at screening for Chlamydia trachomatis or Neisseria gonorrhea

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DARE-PDM1 1% Diclofenac Vaginal Gel; 1% Diclofenac in 2.5 mL Hydrogel	Drug: Diclofenac 1%; vaginal hydrogel containing 1% Diclofenac
Experimental: DARE-PDM1 3% Diclofenac Vaginal Gel; 3% Diclofenac in 2.5 mL Hydrogel	Drug: Diclofenac 3%; vaginal hydrogel containing 3% Diclofenac
Placebo Comparator: Placebo; 2.5 mL Hydrogel	Drug: Placebo; vaginal hydrogel, no active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure the systemic Level of Diclofenac after a single dose of DARE-PDM1	Evaluate the plasma pharmacokinetics of diclofenac after a single dose of DARE-PDM1	7 days
Measure the systemic Level of Diclofenac after three doses of DARE-PDM1	Evaluate the plasma pharmacokinetics of diclofenac after three doses of DARE-PDM1	3 days
Measure the Vaginal Fluid levels of diclofenac after three doses of DARE-PDM1	Evaluate the vaginal fluid pharmacokinetics of diclofenac after three doses of DARE-PDM1	3 days
Measure the Vaginal Fluid levels of diclofenac after a single dose DARE-PDM1	Evaluate the vaginal fluid pharmacokinetics of diclofenac after a single dose of DARE-PDM1	7 days
Number of participants with abnormal vaginal exam findings.	Compare genital safety of DARE-PDM1 versus placebo through vaginal exams	60 days
Number of participants with abnormal laboratory test results.	Evaluate systemic safety of DARE-PDM1 versus placebo through safety laboratory assessments	60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants that record a decrease in dysmenorrhea associated pain	Evaluate the efficacy of DARE-PDM1 versus placebo in reducing dysmenorrhea associated pain	60 days
Use of Rescue Medications	Evaluate the number of pain medication doses needed while using DARE-PDM1	60 days

Collaborators and Investigators

• Sponsor: Daré Bioscience, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Actual): September 23, 2023
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Menstruation Disturbances; Pelvic Pain; Dysmenorrhea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: DARE-PDM1-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A decision has not yet been made on when or what IPD to share when available.

Drug and device information, study documents

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