Vasomotor Symptoms
Conditions
Keywords
vasomotor symptoms, VMS, asimadoline, perimenopausal, postmenopausal, hot flashes
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.
Interventions
DRUGAsimadoline
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.
Sponsors
Tioga Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 62 Years
Healthy volunteers
No
Inclusion criteria
* Females aged 40-62 years. * Untreated patients (either newly diagnosed with VMS or those with a history of VMS but have not been taking drugs that could have an effect on VMS (e.g., SSRIs, SNRIs, gabapentin, pregabalin, clonidine). * Menopausal OR late perimenopausal according to the following criteria: Criteria for Menopause: * Women who have had a bi-lateral oophorectomy (\> 6 weeks prior); OR * Women with a uterus who have had no vaginal bleeding the past 12 months; OR * Women without a uterus (or women with a uterus who have either a levonorgestrel intrauterine device \[LNG IUD\] or who have had an endometrial ablation) and who still have one or both ovaries, with follicle stimulating hormone (FSH) level \> 40 mIU/mL and estradiol ≤ 50 pg/mL (on at least one of two blood draws two weeks apart); Criteria for Late Perimenopause: * Women with a uterus who have had consecutive intervals of amenorrhea of at least 60 days for three or more cycles (i.e., three consecutive episodes of vaginal bleeding separated by 60 or more days between vaginal bleeding episodes). • At least 40 moderate to severe VMS per week for each of the 2 screening weeks, as reported on daily VMS diaries. * Including at least 6 moderate to severe VMS per day on 4 or more days in each of the 2 screening weeks. * VMS frequency in week 2 cannot drop by more than 50% from the average weekly level reported during week 1. * In general good health as determined by medical history, blood pressure, and heart rate. * Signed informed consent.
Exclusion criteria
* • Use of hormone therapy or hormonal contraceptives (with the exception of the LNG IUD) during the 8 weeks before Screening Visit 1. Use of low-dose vaginal estrogen therapies is allowed, with the exception of vaginal creams used \>3 times a week. * Use of non-hormonal medications that can influence VMS during the 4 weeks before Screening Visit 1, including selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, and clonidine. * Use of marijuana or cannabis-derived products (including THC or CBD in any form other than topical, including smoked, vaporized, or edible) that can affect central thermoregulatory processes, mood and perception of VMS, and potentially have pharmacodynamic interactions with the asimadoline during the 4 weeks before Screening Visit 1 as determined by interview and urine drug test. * Use of supplements or herbal therapies that can affect VMS including black cohosh, red clover, dong quai, evening primrose oil, maca, ginseng, chasteberry, milk thistle, and phytoestrogens during the 4 weeks before Screening Visit 1. * Any current severe or unstable medical illness, including the following: * Hypertension of stage 2 or greater (systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90) * Resting heart rate \>100. * Current cancer diagnosis, except non-melanoma skin cancer, or any findings suggestive of or indicating breast malignancy. * Current abnormal Pap smear, breast exam, or mammogram. * Coronary artery disease, or cerebrovascular disease. * Moderate to severe substance use disorder in the previous 12 months; suicide attempt in the previous 36 months, any major depressive episode within the previous 12 months, or lifetime diagnosis of psychosis or bipolar disorder. * Pregnancy, intending pregnancy, breast feeding. * Current participation in another drug trial or intervention study. * Inability or unwillingness to complete the study procedures. Trial-Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Assessed by Adverse Events, Clinical Laboratory Parameters, and Vital Signs | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Frequency of Moderate to Severe Vasomotor Symptoms (VMS) | Baseline to 8 weeks | The frequency of moderate and severe vasomotor symptoms (VMS) will be measured using participant-completed diaries (paper or electronic) recorded twice daily (morning and evening) from Baseline to Week 8. VMS frequency is defined as the number of moderate or severe hot flashes or night sweats reported per day. Moderate VMS: sensation of heat with sweating, without disruption of activity. Severe VMS: sensation of heat with sweating that causes cessation of activity or awakening at night. The outcome is calculated as the average number of moderate/severe VMS episodes per day, averaged over the 8-week treatment period. Due to protocol-defined eligibility criteria, all participants will report at least 40 moderate/severe VMS episodes per week at baseline. During treatment, the minimum possible observed value is 0 episodes/day. There is no fixed upper limit; values of 20-30 episodes/day may occur. Higher values indicate worse symptom frequency. |
| Change in Severity-Weighted Vasomotor Symptom (VMS) Score (Composite Severity Index). | Baseline to 8 weeks | VMS severity will be assessed using a composite score derived from participant diaries recorded twice daily from Baseline to Week 8. Each VMS episode is assigned a severity score: Mild = 1 Moderate = 2 Severe = 3 Daily VMS severity scores are calculated as: (# Mild × 1) + (# Moderate × 2) + (# Severe × 3) Weekly averages of daily severity scores are computed for each participant. The average across the 8-week treatment period will serve as the outcome measure. Due to protocol-defined eligibility criteria, all participants will report ≥40 moderate/severe VMS episodes per week at baseline. During treatment, the minimum possible observed value is 0. There is no fixed upper limit; for example, 10 severe episodes per day would result in a score of 30. Higher scores indicate worse symptom severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Outcome Measure - Change in Female Sexual Function Index (FSFI) Score. | Baseline to 8 weeks | Sexual functioning will be assessed using the FSFI questionnaire, a validated 19-item instrument covering desire, arousal, lubrication, orgasm, satisfaction, and pain. FSFI will be administered at Baseline and Week 8. Scale total range: 2 to 36 Minimum = 2 Maximum = 36 Higher scores indicate better sexual functioning. |
| Exploratory Outcome Measure - Change in Pain Intensity Rating. | Baseline to 8 weeks | Pain intensity will be assessed via participant self-report using a numeric rating scale (NRS), recorded at Baseline and Week 8. Participants will rate the severity of pain symptoms potentially associated with menopausal status or treatment effect. Minimum score: 0 (no pain) Maximum score: 10 (worst pain imaginable) Higher scores indicate worse pain. |
| Exploratory Outcome Measure - Change in Follicle Stimulating Hormone (FSH) Level. | Baseline to 8 weeks | Serum follicle stimulating hormone (FSH) levels will be measured at Baseline and Week 8 to assess hormonal changes related to treatment. Units: mIU/mL No fixed minimum or maximum; normal postmenopausal levels typically \>40 mIU/mL Directional hypothesis: decreasing FSH may correlate with treatment response. |
| Exploratory Outcome Measure - Change in VMS (vasomotor symptoms) Bothersomeness Score | Baseline to 8 weeks | Participant-reported bothersomeness of vasomotor symptoms (VMS) will be assessed using a numeric rating scale completed twice daily (morning and evening) via VMS diaries from Baseline to Week 8. Scale: 0 (not bothersome at all) to 10 (extremely bothersome) Minimum = 0 Maximum = 10 Higher scores indicate greater VMS-related bother. |
| Exploratory Outcome Measure - Change in C-Reactive Protein (CRP) Level | Baseline to 8 weeks | High-sensitivity CRP (hsCRP) will be measured at Baseline and Week 8 as a marker of systemic inflammation. Units: mg/L Typical reference range: \<3.0 mg/L Changes will be evaluated for correlation with treatment response. |
| Exploratory Outcome Measure - Change in Leptin Level. | Baseline to 8 weeks | Serum leptin will be measured at Baseline and Week 8 to evaluate metabolic and hypothalamic correlates of treatment effect. Units: ng/mL |
| Exploratory Outcome Measure - Change in Adiponectin Level | Baseline to 8 weeks | Serum adiponectin will be measured at Baseline and Week 8 to explore its correlation with VMS treatment response. Units: μg/mL Directional hypothesis: modulation may indicate metabolic effects of treatment Higher or lower values will be analyzed for association with response. |
| Exploratory Outcome Measure - Change in Sleep Quality Rating | Baseline to 8 weeks | Sleep quality will be assessed via participant-reported ratings recorded in daily VMS diaries twice daily (morning and evening) from Baseline to Week 8. Participants will indicate the degree to which VMS disrupted their sleep using a 0-10 numeric scale. Minimum score: 0 (no disruption to sleep) Maximum score: 10 (extreme disruption to sleep) Higher scores indicate worse sleep quality. |
| Exploratory Outcome Measure - Change in Menopause-Specific Quality of Life (MENQOL) Score. | Baseline to 8 weeks | Quality of life will be measured using the MENQOL questionnaire, a validated 29-item scale assessing four domains: vasomotor, psychosocial, physical, and sexual. Participants will complete the MENQOL at baseline and at Week 8. Scale range per item: 1 (not at all bothered) to 8 (extremely bothered) Overall score = mean of all item responses Minimum = 1 Maximum = 8 Higher scores indicate worse menopause-related quality of life. |
Countries
United States
Contacts
Primary ContactStandish Fleming, CEO, MBA
Backup ContactGaret Heintz, Regulatory Consultant and Agent, RAC
Outcome results
None listed