Safety and Efficacy of Asimadoline (TP0052) in Patients With Vasomotor Symptoms (VMS).

NCT07042516 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: TIOGA VMS-08IND#: 160,058IRB Tracking Number: 20250414
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Vasomotor Symptoms

Keywords

vasomotor symptoms; VMS; asimadoline; perimenopausal; postmenopausal; hot flashes

Outcome Measures

Primary Outcomes (1)

• Safety as Assessed by Adverse Events, Clinical Laboratory Parameters, and Vital Signs

  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.

  baseline to 8 weeks

Secondary Outcomes (2)

• 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

Other Outcomes (9)

• Exploratory Outcome Measure - Change in VMS (vasomotor symptoms) Bothersomeness Score

  Baseline to 8 weeks

• Exploratory Outcome Measure - Change in Sleep Quality Rating

  Baseline to 8 weeks

• Exploratory Outcome Measure - Change in Menopause-Specific Quality of Life (MENQOL) Score.

  Baseline to 8 weeks

Study Arms (2)

Asimadoline

EXPERIMENTAL

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.

Drug: Asimadoline

Placebo

PLACEBO COMPARATOR

Placebo two (2) tablets bid (two on awakening and two before bed), total of four (4) tablets daily for 8 weeks.

Drug: Asimadoline

Interventions

Asimadoline DRUG

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.

Also known as: TP0052

Asimadoline; Placebo

Eligibility Criteria

• Age: 40 Years - 62 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Known hypersensitivity to asimadoline TP0052.

Sponsors & Collaborators

• Tioga Pharmaceuticals: lead

Study Sites (1)

Department of Gynecology & Obstetrics, Emory University School of Medicine

Atlanta, Georgia, 30329, United States

RECRUITING

Related Publications (40)

• National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):1003-13. Epub 2005 May 27. No abstract available.

  PMID: 15968015 BACKGROUND

• Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.

  PMID: 15082697 BACKGROUND

• Avis NE, Stellato R, Crawford S, Bromberger J, Ganz P, Cain V, Kagawa-Singer M. Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Soc Sci Med. 2001 Feb;52(3):345-56. doi: 10.1016/s0277-9536(00)00147-7.

  PMID: 11330770 BACKGROUND

• Appling S, Paez K, Allen J. Ethnicity and vasomotor symptoms in postmenopausal women. J Womens Health (Larchmt). 2007 Oct;16(8):1130-8. doi: 10.1089/jwh.2006.0033.

  PMID: 17937565 BACKGROUND

• Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric. 2007 Jun;10(3):197-214. doi: 10.1080/13697130601181486.

  PMID: 17487647 BACKGROUND

• 35. NCT02475447, Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Pruritus Associated With Atopic Dermatitis. 2017, Tioga Pharmaceuticals: https://clinicaltrials.gov.

  BACKGROUND

• Mangel AW, Hicks GA. Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review. Clin Exp Gastroenterol. 2012;5:1-10. doi: 10.2147/CEG.S23274. Epub 2012 Jan 12.

  PMID: 22346361 BACKGROUND

• Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro VM, Clifton DK, Mori Y, Tsukamura H, Maeda K, Steiner RA, Okamura H. Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci. 2010 Feb 24;30(8):3124-32. doi: 10.1523/JNEUROSCI.5848-09.2010.

  PMID: 20181609 BACKGROUND

• Trower M, Anderson RA, Ballantyne E, Joffe H, Kerr M, Pawsey S. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause. 2020 May;27(5):498-505. doi: 10.1097/GME.0000000000001500.

  PMID: 32068688 BACKGROUND

• Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, English M, Franklin C, Lee M, Neal-Perry G. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102. doi: 10.1016/S0140-6736(23)00085-5. Epub 2023 Mar 13.

  PMID: 36924778 BACKGROUND

• Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M, Stute P, Thurston RC, Wolfman W, English M, Franklin C, Lee M, Santoro N. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab. 2023 Jul 14;108(8):1981-1997. doi: 10.1210/clinem/dgad058.

  PMID: 36734148 BACKGROUND

• Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR, Mohideen P, Panay N, Hunter MS, Veldhuis JD, Webber LC, Huson L, Dhillo WS. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 6;389(10081):1809-1820. doi: 10.1016/S0140-6736(17)30823-1. Epub 2017 Apr 3.

  PMID: 28385352 BACKGROUND

• Rance NE, Dacks PA, Mittelman-Smith MA, Romanovsky AA, Krajewski-Hall SJ. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013 Aug;34(3):211-27. doi: 10.1016/j.yfrne.2013.07.003. Epub 2013 Jul 17.

  PMID: 23872331 BACKGROUND

• Oakley AE, Steiner RA, Chavkin C, Clifton DK, Ferrara LK, Reed SD. kappa Agonists as a novel therapy for menopausal hot flashes. Menopause. 2015 Dec;22(12):1328-34. doi: 10.1097/GME.0000000000000476.

  PMID: 25988798 BACKGROUND

• 26. FDA, BRISDELLE (paroxetine mesylate) NDA 204516 Approval Letter. U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 2013.

  BACKGROUND

• Joffe H, Guthrie KA, LaCroix AZ, Reed SD, Ensrud KE, Manson JE, Newton KM, Freeman EW, Anderson GL, Larson JC, Hunt J, Shifren J, Rexrode KM, Caan B, Sternfeld B, Carpenter JS, Cohen L. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial. JAMA Intern Med. 2014 Jul;174(7):1058-66. doi: 10.1001/jamainternmed.2014.1891.

  PMID: 24861828 BACKGROUND

• Freeman EW, Guthrie KA, Caan B, Sternfeld B, Cohen LS, Joffe H, Carpenter JS, Anderson GL, Larson JC, Ensrud KE, Reed SD, Newton KM, Sherman S, Sammel MD, LaCroix AZ. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011 Jan 19;305(3):267-74. doi: 10.1001/jama.2010.2016.

  PMID: 21245182 BACKGROUND

• Barton DL, Loprinzi CL, Novotny P, Shanafelt T, Sloan J, Wahner-Roedler D, Rummans TA, Christensen B, Dakhill SR, Martin LS. Pilot evaluation of citalopram for the relief of hot flashes. J Support Oncol. 2003 May-Jun;1(1):47-51.

  PMID: 15352642 BACKGROUND

• Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA, Halyard MY, Pruthi S, Novotny PJ, Rummans TA. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002 Mar 15;20(6):1578-83. doi: 10.1200/JCO.2002.20.6.1578.

  PMID: 11896107 BACKGROUND

• Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol. 2007 Feb;196(2):97-106. doi: 10.1016/j.ajog.2006.05.056.

  PMID: 17306645 BACKGROUND

• Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, Tapanainen JS. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 2005 Jan-Feb;12(1):18-26. doi: 10.1097/00042192-200512010-00006.

  PMID: 15668596 BACKGROUND

• Grady D, Cohen B, Tice J, Kristof M, Olyaie A, Sawaya GF. Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial. Obstet Gynecol. 2007 Apr;109(4):823-30. doi: 10.1097/01.AOG.0000258278.73505.fa.

  PMID: 17400842 BACKGROUND

• Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, Ullmer L, Gallagher A, Cullen J, Gehan E, Hayes DF, Isaacs C. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005 Oct 1;23(28):6919-30. doi: 10.1200/JCO.2005.10.081.

  PMID: 16192581 BACKGROUND

• Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000 Dec 16;356(9247):2059-63. doi: 10.1016/S0140-6736(00)03403-6.

  PMID: 11145492 BACKGROUND

• Shaver JL. Beyond hormonal therapies in menopause. Exp Gerontol. 1994 May-Aug;29(3-4):469-76. doi: 10.1016/0531-5565(94)90027-2.

  PMID: 7925765 BACKGROUND

• Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes D. Hot flushes. Lancet. 2002 Dec 7;360(9348):1851-61. doi: 10.1016/s0140-6736(02)11774-0.

  PMID: 12480376 BACKGROUND

• Freedman RR, Woodward S, Sabharwal SC. Alpha 2-adrenergic mechanism in menopausal hot flushes. Obstet Gynecol. 1990 Oct;76(4):573-8.

  PMID: 2170883 BACKGROUND

• 13. Freedman, R. and S. Woodward, Elevated α2-adrenergic responsiveness in menopausal hot flushes: pharmacologic and biochemical studies. Thermoregulation: the pathophysiological basis of clinical disorders. Basel: Karger, 1992: p. 6-9.

  BACKGROUND

• Bruck K, Zeisberger E. Adaptive changes in thermoregulation and their neuropharmacological basis. Pharmacol Ther. 1987;35(1-2):163-215. doi: 10.1016/0163-7258(87)90106-9.

  PMID: 3321099 BACKGROUND

• 11. Freedman, R.R. Pathophysiology and treatment of menopausal VMS. in Seminars in reproductive medicine. 2005. Copyright© 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

  BACKGROUND

• 10. FDA, VEOZAH™ (fezolinetant) tablets, for oral use: NDA 216578 Approval Letter. U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 2023.

  BACKGROUND

• Simon JA, Portman DJ, Kaunitz AM, Mekonnen H, Kazempour K, Bhaskar S, Lippman J. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013 Oct;20(10):1027-35. doi: 10.1097/GME.0b013e3182a66aa7.

  PMID: 24045678 BACKGROUND

• Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician. 2006 Feb 1;73(3):457-64.

  PMID: 16477892 BACKGROUND

• Geller SE, Studee L. Botanical and dietary supplements for mood and anxiety in menopausal women. Menopause. 2007 May-Jun;14(3 Pt 1):541-9. doi: 10.1097/01.gme.0000236934.43701.c5.

  PMID: 17194961 BACKGROUND

• Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79. doi: 10.7326/0003-4819-145-12-200612190-00003.

  PMID: 17179056 BACKGROUND

• Tremblay A, Sheeran L, Aranda SK. Psychoeducational interventions to alleviate hot flashes: a systematic review. Menopause. 2008 Jan-Feb;15(1):193-202. doi: 10.1097/gme.0b013e31805c08dc.

  PMID: 17589375 BACKGROUND

• Buist DS, Newton KM, Miglioretti DL, Beverly K, Connelly MT, Andrade S, Hartsfield CL, Wei F, Chan KA, Kessler L. Hormone therapy prescribing patterns in the United States. Obstet Gynecol. 2004 Nov;104(5 Pt 1):1042-50. doi: 10.1097/01.AOG.0000143826.38439.af.

  PMID: 15516400 BACKGROUND

• Haas JS, Kaplan CP, Gerstenberger EP, Kerlikowske K. Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med. 2004 Feb 3;140(3):184-8. doi: 10.7326/0003-4819-140-3-200402030-00009.

  PMID: 14757616 BACKGROUND

• Grady D, Ettinger B, Tosteson AN, Pressman A, Macer JL. Predictors of difficulty when discontinuing postmenopausal hormone therapy. Obstet Gynecol. 2003 Dec;102(6):1233-9. doi: 10.1016/j.obstetgynecol.2003.09.025.

  PMID: 14662209 BACKGROUND

• Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.

  PMID: 12117397 BACKGROUND

MeSH Terms

Conditions

Hot Flashes

Interventions

asimadoline

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anne Dunlop - Principal Investigator, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Sergey Sikora, VP of Clinical Affairs, PhD

  Tioga Pharmaceuticals

  STUDY CHAIR

Central Study Contacts

Standish Fleming, CEO, MBA

CONTACT

(858) 245-7563; fleming@tiogapharma.com

Garet Heintz, Regulatory Consultant and Agent, RAC

CONTACT

858-571-1800; gheintz@therapeuticsinc.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: June 29, 2025
• Study Start: August 13, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 20, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (1)