Safety and Efficacy of Asimadoline (TP0052), a Peripherally Restricted Selective Kappa Agonist, for the Treatment of Moderate to Severe Menopausal Symptoms in Midlife Women.
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Safety as Assessed by Adverse Events, Clinical Laboratory Parameters, and Vital Signs
Study Overview
Brief Summary
This Randomized Clinical Trial entitled Safety and Efficacy of a Peripherally Restricted Selective Kappa Agonist for Moderate to Severe Menopausal Symptoms in Midlife Women is a Phase 2a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of asimadoline TP0052 for the treatment of moderate to severe menopausal vasomotor symptoms (VMS). The design includes: 2 weeks of daily recording of VMS prior to drug treatment; 8 weeks of double-blind treatment with the peripherally restricted kappa agonist (PRKA), asimadoline TP0052, or placebo; and a safety telephone follow-up post-treatment; after the initial 8-week double-blinded follow-up, all patients undergo treatment with Asimadoline in an open label format for 4 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Sponsor
Eligibility Criteria
- Ages
- 40 Years to 62 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Known hypersensitivity to asimadoline TP
- •Chronic liver or renal disease, or uncontrolled seizure disorder.
- •Use of medications or supplements that act as an inhibitor of P-glycoprotein or as a P-glycoprotein substrate during the 4 weeks prior to Screening Visit 1, including cyclosporine, non-topical ketoconazole, verapamil, digoxin, colchicine, sitagliptin).
- •Blood test results indicating:
- •Liver function tests: AST ≥2 times upper limit of normal; ALT ≥2 times upper limit of normal; total bilirubin ≥ 1.5 times upper limit of normal
- •Kidney function test: estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²
- •Blood count: hematocrit <30%.
Arms & Interventions
Asimadoline
Asimadoline TP0052 2.5 mg two (2) tablets bid (two on awakening and two before bed), total of four (4) tablets daily (10 mg) for 8 weeks. Post-unblinding 4 weeks of open label administration, TP0052 2.5 mg two (2) tablets bid (two on awakening and two before bed), total of four (4) tablets daily (10 mg) for 4 weeks.
Intervention: Asimadoline (Drug)
Placebo
Placebo two (2) tablets bid (two on awakening and two before bed), total of four (4) tablets daily for 8 weeks.
Intervention: Asimadoline (Drug)
Outcomes
Primary Outcomes
Safety as Assessed by Adverse Events, Clinical Laboratory Parameters, and Vital Signs
Time Frame: baseline to 8 weeks
Safety will be evaluated based on the incidence and severity of adverse events and changes from baseline in laboratory values and vital signs. Adverse events will be graded using the Common Terminology Criteria for Adverse Events, Version 5.0 (grade 1 = mild; grade 5 = death; higher scores indicate worse outcomes). Liver function tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and total bilirubin. Higher values indicate worse liver function. Kidney function will be assessed by estimated glomerular filtration rate (scale: 0 to ≥90 mL/min/1.73 m²; \<60 considered abnormal; higher is better). Hematocrit will be monitored (percent; \<30% is abnormal; higher is better within normal range). Vital signs include blood pressure, heart rate, respiratory rate, and oral temperature; higher blood pressure and heart rate indicate worse outcomes. A urine pregnancy test (positive or negative) will also be performed.
Secondary Outcomes
- Change in Frequency of Moderate to Severe Vasomotor Symptoms (VMS)(Baseline to 8 weeks)
- Change in Severity-Weighted Vasomotor Symptom (VMS) Score (Composite Severity Index).(Baseline to 8 weeks)