ITT-5 Mechanisms of Spermatogenesis in Man

NCT02147964 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: STUDY00001449
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this investigational drug study is to determine how much male hormone, testosterone, is needed to maintain sperm production in the testis.

Conditions

Gonadotropin Deficiency

Keywords

intratesticular androgens; testosterone; dutasteride; gonadotropin suppression; male contraception; spermatogenesis

Outcome Measures

Primary Outcomes (1)

• Sperm concentration

  Difference in sperm concentration at week 16 between 4 treatment groups

  16 weeks

Secondary Outcomes (1)

• IT steroid concentration

  16 weeks

Study Arms (4)

Acyline; T Gel; placebo dutasteride, placebo ketoconazole

EXPERIMENTAL

All men will receive Acyline 300 ug/kg subcutaneous (SQ) injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 1: placebo oral ketoconazole + placebo oral dutasteride for 4 months

Drug: Testosterone 1% Gel; Drug: Acyline; Drug: placebo dutasteride; Drug: placebo ketoconazole

Acyline; T gel; Ketoconazole; placebo

EXPERIMENTAL

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 2: oral ketoconazole 400 mg + placebo oral dutasteride for 4 months

Drug: Testosterone 1% Gel; Drug: Acyline; Drug: Ketoconazole; Drug: placebo dutasteride

Acyline; Tgel; Ketoconazole; Dutasteride

EXPERIMENTAL

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 3: Ketoconazole 400mg orally daily + Dutasteride 2.5 mg orally on day 1, followed by 0.5mg daily for 4 months

Drug: Testosterone 1% Gel; Drug: Acyline; Drug: Dutasteride; Drug: Ketoconazole

Acyline; Tgel; HCG

EXPERIMENTAL

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 4: Human Chorionic gonadotropin (HCG) 60 IU injection every other day for 4 months.

Drug: Testosterone 1% Gel; Drug: Acyline; Drug: HCG

Interventions

Testosterone 1% Gel DRUG

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Also known as: T gel, Testosterone gel, AndroGel

Acyline; T Gel; placebo dutasteride, placebo ketoconazole; Acyline; T gel; Ketoconazole; placebo; Acyline; Tgel; HCG; Acyline; Tgel; Ketoconazole; Dutasteride

Acyline DRUG

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

Acyline; T Gel; placebo dutasteride, placebo ketoconazole; Acyline; T gel; Ketoconazole; placebo; Acyline; Tgel; HCG; Acyline; Tgel; Ketoconazole; Dutasteride

Dutasteride DRUG

Dutasteride 2.5 mg (day 1) followed by 0.5 mg daily for 4 months

Also known as: Avodart

Acyline; Tgel; Ketoconazole; Dutasteride

Ketoconazole DRUG

ketoconazole 400 mg PO daily for 4 months

Acyline; T gel; Ketoconazole; placebo; Acyline; Tgel; Ketoconazole; Dutasteride

HCG DRUG

HCG 60 IU injection Subcutaneously, every other day for 4 months

Also known as: Human chorionic gonadotropin (HCG)

Acyline; Tgel; HCG

placebo dutasteride DRUG

placebo oral dutasteride PO daily for 4 months

Acyline; T Gel; placebo dutasteride, placebo ketoconazole; Acyline; T gel; Ketoconazole; placebo

placebo ketoconazole DRUG

placebo ketoconazole daily for 4 months

Acyline; T Gel; placebo dutasteride, placebo ketoconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males age 18-55
• In general good health based on normal screening evaluation
• Normal serum testosterone, lutenizing hormone (LH) and follicle stimulating hormone (FSH)
• Prostate Specific Antigen (PSA) \< 3.0
• Agrees not to donate blood or participate in another research study during the study
• Informed consent
• Must be willing to use a reliable form of contraception during the study

You may not qualify if:

• Participation in a long-term male contraceptive study within the past three months
• History of testosterone or anabolic steroid abuse in the past
• History of or current skin disorder that will interfere with testosterone gel
• Poor general health or significantly abnormal screening blood results
• History of or current testicular or prostate disease
• History of a bleeding disorder or need for anticoagulation
• History of untreated sleep apnea and/or major psychiatric problems
• BMI \> 32
• History of or current liver disease
• Chronic pain syndrome
• Current use of terfenidine, astemizole, cisapride, budesonide, felodipine, fluticasone, lovastatin, midazolam, sildenafil, or vardenafil
• Use of glucocorticoids or underlying adrenal insufficiency
• Active drug or alcohol abuse within the past year

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington Medical Center (Health Sciences)

Seattle, Washington, 98195, United States

Location

Related Publications (12)

• Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990 Oct 20;336(8721):955-9.

  PMID: 1977002 BACKGROUND

• Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1996 Mar;65(3):626-36.

  PMID: 8774299 BACKGROUND

• Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14.

  PMID: 10386821 BACKGROUND

• Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989 Jun;124(6):3043-9. doi: 10.1210/endo-124-6-3043.

  PMID: 2498065 BACKGROUND

• Roth MY, Lin K, Amory JK, Matsumoto AM, Anawalt BD, Snyder CN, Kalhorn TF, Bremner WJ, Page ST. Serum LH correlates highly with intratesticular steroid levels in normal men. J Androl. 2010 Mar-Apr;31(2):138-45. doi: 10.2164/jandrol.109.008391. Epub 2009 Sep 24.

  PMID: 19779211 BACKGROUND

• Roth MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Snyder CN, Marck BT, Bremner WJ, Amory JK. Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency. J Clin Endocrinol Metab. 2010 Aug;95(8):3806-13. doi: 10.1210/jc.2010-0360. Epub 2010 May 19.

  PMID: 20484472 BACKGROUND

• Trachtenberg J, Zadra J. Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5.

  PMID: 2966691 BACKGROUND

• Nashan D, Knuth UA, Weidinger G, Nieschlag E. The antimycotic drug terbinafine in contrast to ketoconazole lacks acute effects on the pituitary-testicular function of healthy men: a placebo-controlled double-blind trial. Acta Endocrinol (Copenh). 1989 May;120(5):677-81. doi: 10.1530/acta.0.1200677.

  PMID: 2499150 BACKGROUND

• Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE, Stevens DA. High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med. 1984 Nov;144(11):2150-3.

  PMID: 6093722 BACKGROUND

• Van Tyle JH. Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use. Pharmacotherapy. 1984 Nov-Dec;4(6):343-73. doi: 10.1002/j.1875-9114.1984.tb03398.x.

  PMID: 6151171 BACKGROUND

• Roth MY, Nya-Ngatchou JJ, Lin K, Page ST, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Amory JK. Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole. J Clin Endocrinol Metab. 2013 Mar;98(3):1198-206. doi: 10.1210/jc.2012-3527. Epub 2013 Jan 24.

  PMID: 23348398 BACKGROUND

• Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. 2005 May;90(5):2595-602. doi: 10.1210/jc.2004-0802. Epub 2005 Feb 15.

  PMID: 15713727 BACKGROUND

MeSH Terms

Conditions

Hypogonadism

Interventions

Testosterone; Gels; Coal Tar; acyline; Dutasteride; Ketoconazole; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Tars; Azasteroids; Steroids, Heterocyclic; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropins; Peptide Hormones; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins

Study Officials

• Mara Roth, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

• William J Bremner, MD, PhD

  University of Washington

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: May 28, 2014
• Study Start: June 1, 2019
• Primary Completion: December 1, 2021
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

US (1)