Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Injectable DMAU for Male Contraception in Healthy Male Volunteers (CCN015) (DMAU)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02927210
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
University of Washington
Information provided by (Responsible Party):
Health Decisions

Tracking Information
First Submitted Date  ICMJE September 28, 2016
First Posted Date  ICMJE October 6, 2016
Last Update Posted Date August 12, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Incidence of treatment emergent adverse events (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in sexual function (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) using the psychosexual daily questionnaire [ Time Frame: 5-7 months ]
  • Changes from baseline in mood (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) using the Patient Health Questionnaire-9 [ Time Frame: 5-7 months ]
  • Changes from baseline in sodium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in potassium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in chloride (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in bicarbonate (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in fasting glucose (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in blood urea nitrogen (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in creatinine (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in calcium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in total bilirubin (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in alkaline phosphatase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in alanine aminotransferase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in aspartate transaminase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in albumin (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in blood pressure (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in pulse (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in respiratory rate (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
  • Changes from baseline in body mass index (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) [ Time Frame: 5-7 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02927210 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Pharmacokinetics of DMAU and DMA using AUC (0-t, where t is the last time-point with measurable concentration) [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of serum Testosterone (T) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of Dihydrotestosterone (DHT) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of Estradiol (E2) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of Follicle Stimulating Hormone (FSH) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of Luteinizing Hormone (LH) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of Sex Hormone Binding Globulin (SHBG) using mean values at each visit [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of serum T using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of serum T using percentage of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of DHT using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of DHT using percentage of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of E2 using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of E2 using percentage of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of FSH using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of FSH using of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of LH using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of LH using percentage of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of SHBG using number of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Pharmacodynamics of DMAU by assessing the suppression of SHBG using percentage of subjects with FSH and LH ≤ 1.0 IU/L [ Time Frame: 5-7 months ]
  • Suppression of spermatogenesis as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL [ Time Frame: 5-7 months ]
  • Suppression of spermatogenesis as assessed by semen analyses using percentage of subjects with sperm concentration <1 million (M)/mL [ Time Frame: 5-7 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Injectable DMAU for Male Contraception in Healthy Male Volunteers (CCN015)
Official Title  ICMJE Injectable DMAU for Male Contraception: Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of Single IM or SC DMAU Injection Dose Escalation Study in Healthy Male Volunteers
Brief Summary This is a Phase I multicenter, double-blind, single dose, dose-ranging study, in healthy men to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of Dimethandrolone Undecanoate (DMAU) administered as an intramuscular or subcutaneous injection.
Detailed Description

This single dose, dose-ranging study will be conducted in two centers: the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of Washington.

Single doses of DMAU in castor oil/benzyl benzoate injections intramuscularly (IM) (80 mg, 240 mg, 480 mg, and 800 mg) or administered subcutaneously (SC) (50 mg, 100 mg and 200 mg) were selected for this dose-escalating study. Twelve subjects will complete this study at each of the DMAU doses (10 on DMAU and 2 on placebo injections) yielding a total of 84 completed subjects (70 on DMAU and 14 on placebo) across both sites. Safety will be assessed in all subjects and recovery will be assessed in two subjects receiving lower doses, either IM or SC, before additional men receive higher doses of IM or SC of DMAU. In addition to safety and tolerability, suppression of serum T, E2, gonadotropins, and SHBG will be assessed as secondary pharmacodynamic (PD) endpoints. PK of DMAU and DMA will be assessed through blood draws done at each visit. Suppression of spermatogenesis will be assessed with semen analysis.

DMAU injections will be administered at the study site by research nurses or physicians. For intramuscular injections, the staff will inject DMAU in castor oil into the gluteal region following standard procedures for intramuscular steroid injection. Abdominal subcutaneous injections will follow standard subcutaneous procedures. The subject will be observed for at least 30 minutes before release from the study site.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE
  • Healthy Men
  • Male Contraception
Intervention  ICMJE
  • Drug: Dimethandrolone Undecanoate
    Single doses of DMAU in castor oil/benzyl benzoate injections intramuscularly (IM) (80 mg, 240 mg, 480 mg, and 800 mg) or administered subcutaneously (SC) (50 mg, 100 mg and 200 mg).
    Other Name: DMAU
  • Drug: Placebo
    Placebo injections that look like the DMAU injections but with no active ingredients
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo injections that look like the DMAU injections but with no active ingredients
    Intervention: Drug: Placebo
  • Experimental: Dimethandrolone Undecanoate
    Single doses of DMAU administered via injection intramuscularly (IM - 80 mg, 240 mg, 480 mg, and 800 mg) or administered subcutaneously (SC - 50 mg, 100 mg and 200 mg)
    Intervention: Drug: Dimethandrolone Undecanoate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2017)
84
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2016)
72
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Men who meet all the following criteria are eligible for enrollment in the trial:

  1. Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of screening.
  2. 18 to 50 years of age (inclusive) at the time of the enrollment visit.
  3. BMI ≤ 33 calculated as weight in kg/ (height in m2).
  4. Weight ≥60 kg.
  5. No history of hormonal therapy use in the three months prior to the first screening visit.
  6. Agree to use a recognized effective method of contraception with any female partner (i.e. at a minimum, barrier plus an additional method of contraception) during the course of the study treatment and recovery phases until recovery is confirmed and study exit occurs.
  7. Subjects will refrain from donating blood or plasma during the study period.
  8. Subjects will be advised to refrain from excessive alcoholic consumption during the study period. (No more than 15 drinks per week and no alcohol consumption within 24 hours of a study visit.)
  9. No known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance.
  10. In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form.

12. Subjects will be advised to refrain from major changes in their level of exercise during the study period.

Exclusion Criteria:

Men who meet any of the following criteria are NOT eligible for enrollment in the trial:

  1. Men participating in another clinical trial involving an investigational drug within the 30 days prior to the first screening visit.
  2. Men not living in the catchment area of the clinic or within a reasonable distance from the study site.
  3. Clinically significant abnormal physical and laboratory findings at screening.
  4. Elevated PSA (levels ≥ 2.5 ng/mL) at screening, according to local laboratory normal values.
  5. Abnormal serum chemistry values at screening, according to local laboratory reference ranges that indicate liver or kidney dysfunction or that may be considered clinically significant. In addition, the following upper limits will be observed: fasting bilirubin less than 2 mg/dL, cholesterol less than 221 mg/dL, and fasting triglycerides less than 201 mg/dL.
  6. Abnormal semen analyses or abnormal semen concentration as defined by the WHO semen manual.
  7. Use of androgens within 3 months before first screening visit except for long acting testosterone injections (e.g. Testosterone undecanoate) which will require a wash out period of 6 months prior to screening.
  8. Ongoing use of body building substances including nutritional supplements.
  9. Systolic BP > 130 mm Hg and Diastolic blood pressure BP > 80 and mm Hg; Blood pressure (BP) will be taken 3 times at 5 - minute intervals and the mean of all measurements be used to determine eligibility).
  10. Clinically significant abnormal EKG or a QTc interval of > 450 msec.
  11. PHQ-9 score of 15 or above.
  12. History of hypertension, including hypertension controlled with treatment.
  13. Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
  14. Benign or malignant liver tumors; active liver disease.
  15. History of breast carcinoma.
  16. Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease.
  17. Known history of cardiovascular, renal, hepatic or prostatic disease or significant psychiatric illness.
  18. Positive serology for active Hepatitis (not immunization-related serology) or HIV at screening visit.
  19. A serious systemic disease such as diabetes mellitus or obesity (body weight greater than BMI >33 kg/m2 as above).
  20. History of known, untreated sleep apnea.

22. Partner is known to be pregnant. 23. Men desiring fertility within the first seven months of study participation.

24. Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine. Exclusion is due to the potential of testing positive for androgens that may occur from their study participation coupled with the unknown efficacy (i.e. duration of positive testing) from a single injection.

26. Use of sex steroids or medications which might interfere with steroid metabolism (i.e. ketoconazole, finasteride, oral corticosteroids, dutasteride and statins).

27. Use of medications that will interfere or interact with DMAU.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Christina Wang, MD 310-222-2503 wang@labiomed.org
Contact: Stephanie Page, MD, PhD 206-616-1818 page@uw.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02927210
Other Study ID Numbers  ICMJE CCN015
HHSN275201200002I ( Other Grant/Funding Number: NICHD Contract. This is not a grant but a contract. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Health Decisions
Study Sponsor  ICMJE Health Decisions
Collaborators  ICMJE
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • University of Washington
Investigators  ICMJE
Principal Investigator: Christina Wang, MD Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Principal Investigator: Stephanie Page Page, MD, PhD University of Washington
PRS Account Health Decisions
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP