A Study of Diclofenac Gel in Women With Primary Dysmenorrhea

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Dysmenorrhea Primary

Intervention / Treatment
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* Drug: Diclofenac 1%
* Drug: Diclofenac 3%
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

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
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |