Study of VERU-944 to Ameliorate Hot Flashes in Men With Advanced Prostate Cancer

Randomized, Double-blind, Placebo Controlled, Dose Finding Phase 2 Study Comparing Oral Daily Dosing of VERU-944 to Ameliorate the Vasomotor Symptoms Resulting From ADT in Men With Advanced Prostate Cancer

Randomized, double-blind, placebo controlled, dose finding Phase 2 study comparing oral daily dosing of VERU-944 after a week of loading (daily dosing) with placebo to ameliorate the vasomotor symptoms resulting from androgen deprivation therapy in men with advanced prostate cancer

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Drug: Placebo; Drug: Veru-944

Detailed Description

This study is a multicenter, randomized, double-blind, placebo controlled, dose finding study of VERU-944 to treat hot flashes (vasomotor symptoms) in men with advanced prostate cancer on ADT. The study will have four arms with 30 subjects per arm. The subjects participating in the study will have advanced prostate cancer and will be undergoing androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone (LHRH) therapy (agonist or antagonist) for at least the three months prior to randomization and be experiencing regular moderate to severe hot flashes while on ADT. Subjects will all continue to receive ADT and will be randomized to receive, for the first four days, a loading dose followed by daily doses of placebo or VERU-944 (10 mg, 50 mg or 100 mg) orally for a total period of 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Gen1 Research
  • California
    • Los Angeles, California, United States, 90048
      • Tower Urology
    • San Bernardino, California, United States, 92404
      • Urology of San Bernardino
  • Colorado
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
    • Golden, Colorado, United States, 80401
      • Foothills Urology
  • Florida
    • Doral, Florida, United States, 33166
      • Universal Axon Clinical Research
    • Miami, Florida, United States, 33144
      • Medical Research Center
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Urology
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • First Urology
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Regional Urology LLC
  • Maryland
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Coastal Urology
    • Edison, New Jersey, United States, 08837
      • Premier Urology Group
  • New York
    • Elmont, New York, United States, 11003
      • Advance Urology
    • Garden City, New York, United States, 11530
      • AccuMed Research
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Clinical Research Solutions
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • Houston, Texas, United States, 77091
      • Houston Urology Partners
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria

1. Be over 18 years of age;
2. Be able to communicate effectively with the study personnel;
3. Have histologically confirmed prostate cancer;
4. Have been treated with an LHRH agonist or LHRH antagonist for at least the 3 months prior to randomization;
5. Be continued on an LHRH agonist or LHRH antagonist throughout this study;
6. Have experienced hot flashes for at least one month prior to study entry;
7. Have moderate or severe vasomotor symptoms (hot flashes) (defined as a minimum of 4 moderate to severe hot flashes per day or 12 per week at baseline);
8. ECOG performance status of 0 to 2

9. Be willing to uses electronic data capture for the relevant medical events

   • Must be at least 80% compliant during the screening period

10. Subjects must agree to use acceptable methods of contraception:

    • If their female partners are pregnant or lactating, acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication must be used. Acceptable methods are: Condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia), a condom with spermicidal foam/gel/film/cream/suppository should be used.
    • If the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository).
    • If the female partner has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used.
    • If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used.
11. Subject is willing to comply with the requirements of the protocol through the end of the study.

Exclusion Criteria

1. Have a serum total testosterone concentration > 50 ng/dL at screening;
2. Known hypersensitivity or allergy to estrogen or estrogen like drugs;
3. Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk;
4. Subjects with a personal history of abnormal blood clotting or thrombotic disease, including venous or arterial thrombotic events such as a history of stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE);

5. Any subjects, as determined by a central laboratory, that have a:

   • Factor V Leiden gene mutation
   • Prothrombin gene mutation
6. Uncontrolled symptomatic congestive heart failure (NYHA Class III - IV), unstable angina pectoris, cardiac arrhythmia, or uncontrolled atrial fibrillation;
7. History of MI
8. The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study;
9. Received an investigational drug within a period of 90 days prior to enrollment in the study;
10. Received the study medication (VERU-944) previously;
11. Have previously taken within 6 months prior to screening or are currently taking diethylstilbestrol, other estrogens;
12. Currently taking gabapentin, estrogen, diethylstilbestrol, medroxyprogesterone acetate, clomiphene, selective serotonin reuptake inhibitors (SSRIs), other treatments for hot flashes
13. Recent hospitalization for more than 24 hours (within 30 days of screening);
14. Recent surgery (within 30 days of screening);
15. Have been previously diagnosed or treated for active cancer (other than prostate cancer or non-melanoma skin cancer) within the previous five years;
16. Have a BMI >40.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo daily	Drug: Placebo; Placebo
Experimental: Veru-944 10 mg; Veru-944 10 mg daily	Drug: Veru-944; Treat hot flashes (vasomotor symptoms) in men with advanced prostate cancer on ADT; Other Names: Zuclomiphene citrate
Experimental: Veru-944 50 mg; Veru-944 50 mg daily	Drug: Veru-944; Treat hot flashes (vasomotor symptoms) in men with advanced prostate cancer on ADT; Other Names: Zuclomiphene citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Frequency of Moderate to Severe Hot Flashes at 6 Weeks	Percentage of change in frequency of moderate to severe hot flashes at 6 weeks	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Severity of Moderate to Severe Hot Flashes at 6 Weeks	Change in severity of moderate to severe hot flashes compared to baseline at 6 weeks	6 weeks
Change of Frequency of Moderate to Severe Hot Flashes at Week 12	Mean change in frequency of moderate to severe hot flashes compared to baseline at weeks 12	Weeks 12
Change in Severity of Moderate to Severe Hot Flashes at Week 12	Mean change in severity of moderate to severe hot flashes compared to baseline at week 12	Week 12
Change in Bone Turnover Markers C-telopeptide (CTX)	Change in C-telopeptide concentration at day 84 compared to baseline	84 days
Change in Bone Turnover Markers Alkaline Phosphatase	Change in bone specific alkaline phosphatase at day 84 compared to baseline	84 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum PSA	Change in serum PSA concentration comparing baseline to day 30, baseline to day 60 and baseline to day 84 for each treatment group	84 Days
Change in Serum Total Testosterone	Change in serum total testosterone concentration comparing baseline to day 30, baseline to day 60 and baseline to day 84 for each treatment group	84 Days
Change in Serum Free Testosterone	Change in serum free testosterone concentration comparing baseline to day 84	84 days
Change in Serum SHBG	Change in serum SHBG concentration comparing baseline to day 30, baseline to day 60 and baseline to day 84 for each treatment group	84 days
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)Sess Safety	Incidence of Treatment-Emergent Adverse Events will be tabulated by MedDRA terms and system organ class. The incidence of AEs and the maximum intensity and frequency of AEs will be summarized. The intensity of AE will be graded according to CTCAE version 4. Changes from baseline will be computed and tested for significant change from baseline to day 114	114 days

Collaborators and Investigators

• Sponsor: Veru Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): October 15, 2020

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Zuclomiphene
• Other Study ID Numbers: V72203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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