Pharmacokinetic Evaluation of Serum Testosterone Concentrations After Administration of Clomiphene Citrate

Testosterone Deficiency Clinical Trial

Official title:

Pharmacokinetic Evaluation of Serum Testosterone Concentrations After Administration of Clomiphene Citrate

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05096169
• Other study ID #: 20-10022773
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: January 2025

Study information

• Verified date: December 2023
• Source: Weill Medical College of Cornell University
• Contact: Jonathan Gal, MD
• Phone: 212-746-5470
• Email: jog4018[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, open-label trial examining two doses of clomiphene citrate in men with low serum testosterone concentrations (total testosterone (TT) < 300 ng/dl).

Description:

This is a randomized, open-label trial examining two doses of clomiphene citrate in men with low serum testosterone concentrations (total testosterone (TT) < 300 ng/dl). The investigators will perform a pharmacokinetic analysis of serum hormone concentrations (TT, LH, FSH, estradiol) after medication administration. Researchers hypothesize that testosterone levels will increase in both groups and this may allow to dose clomiphene citrate so that patients do not need to take the medication daily.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male, 21-45 years of age

• Serum testosterone concentration < 300 ng/dl measured on two separate occasions (separated by at least one week), with collection prior to 10AM

Exclusion Criteria:

• Serum testosterone concentration > 300 ng/dl

• Abnormal serum prolactin (PRL) concentration (PRL > 15.2 ng/ml)

• Concurrent or prior use of hormone-modifying medications (clomiphene citrate or other SERM, testosterone replacement therapy or other testosterone-containing products/treatments, gonadotropin therapy, aromatase inhibitors, estrogen-containing products/treatments)

• Documented karyotype abnormality

• Diagnosis of Kallmann syndrome

• Any prior chemotherapy, radiation therapy to the groin/pelvis, or known exposure to gonadotoxic agents

• History of cryptorchidism or prior orchiopexy

• History of testicular cancer or prior orchiectomy

• History of pituitary tumor or resection of pituitary tumor

• History of prostate cancer or severe benign prostatic hypertrophy

• History of epididymitis or epididymo-orchitis, or orchitis (including mumps)

• History of primary hypogonadism

• History of prior urinary tract infection

• History of intravenous drug use

• Any of the following comorbidities: renal insufficiency, heart disease, peptic ulcer disease, cerebrovascular disease, liver disease, psychiatric disorders, chronic pain, bleeding diatheses, anemia, polycythemia, vision problems

• Medical history or concurrent illness that the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial, or constitutes an unacceptable risk to the subject

• Documented allergy or hypersensitivity to clomiphene citrate or other SERM

Related Conditions & MeSH terms

• Testosterone Deficiency

Intervention

Drug:
• Clomiphene Citrate 25mg
clomiphene citrate at a dose of 25mg daily
• Clomiphene Citrate 50mg
clomiphene citrate at a dose of 50mg every other day

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (22)

Adashi EY. Clomiphene citrate: the case for a monoisomeric preparation. Baillieres Clin Obstet Gynaecol. 1993 Jun;7(2):331-47. doi: 10.1016/s0950-3552(05)80134-8. No abstract available. — View Citation

Bendre SV, Murray PJ, Basaria S. Clomiphene Citrate Effectively Increases Testosterone in Obese, Young, Hypogonadal Men. Reprod Syst Sex Disord. 2015 Dec;4(4):155. doi: 10.4172/2161-038X.1000155. Epub 2015 Nov 13. — View Citation

Ernst S, Hite G, Cantrell JS, Richardson A Jr, Benson HD. Stereochemistry of geometric isomers of clomiphene: a correction of the literature and a reexamination of structure-activity relationships. J Pharm Sci. 1976 Jan;65(1):148-50. doi: 10.1002/jps.2600650140. No abstract available. — View Citation

Fontenot GK, Wiehle RD, Podolski JS. Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice. BJU Int. 2016 Feb;117(2):344-50. doi: 10.1111/bju.13244. Epub 2015 Sep 7. — View Citation

Ghobadi C, Mirhosseini N, Shiran MR, Moghadamnia A, Lennard MS, Ledger WL, Rostami-Hodjegan A. Single-dose pharmacokinetic study of clomiphene citrate isomers in anovular patients with polycystic ovary disease. J Clin Pharmacol. 2009 Feb;49(2):147-54. doi: 10.1177/0091270008328096. Epub 2008 Nov 25. — View Citation

Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L Jr. A pharmacological review of selective oestrogen receptor modulators. Hum Reprod Update. 2000 May-Jun;6(3):212-24. doi: 10.1093/humupd/6.3.212. — View Citation

Habous M, Giona S, Tealab A, Aziz M, Williamson B, Nassar M, Abdelrahman Z, Remeah A, Abdelkader M, Binsaleh S, Muir G. Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study. BJU Int. 2018 Nov;122(5):889-897. doi: 10.1111/bju.14401. Epub 2018 Jun 14. — View Citation

Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012 Aug;110(4):573-8. doi: 10.1111/j.1464-410X.2011.10702.x. Epub 2011 Nov 1. — View Citation

Kim MJ, Byeon JY, Kim YH, Kim SH, Lee CM, Jung EH, Chae WK, Lee YJ, Jang CG, Lee SY, Choi CI. Effect of the CYP2D6*10 allele on the pharmacokinetics of clomiphene and its active metabolites. Arch Pharm Res. 2018 Mar;41(3):347-353. doi: 10.1007/s12272-018-1005-7. Epub 2018 Mar 7. — View Citation

Knight JC, Pandit AS, Rich AM, Trevisani GT, Rabinowitz T. Clomiphene-Associated Suicide Behavior in a Man Treated for Hypogonadism: Case Report and Review of The Literature. Psychosomatics. 2015 Sep-Oct;56(5):598-602. doi: 10.1016/j.psym.2015.06.003. Epub 2015 Jun 12. No abstract available. — View Citation

Krzastek SC, Sharma D, Abdullah N, Sultan M, Machen GL, Wenzel JL, Ells A, Chen X, Kavoussi M, Costabile RA, Smith RP, Kavoussi PK. Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism. J Urol. 2019 Nov;202(5):1029-1035. doi: 10.1097/JU.0000000000000396. Epub 2019 Oct 9. — View Citation

Mazzola CR, Katz DJ, Loghmanieh N, Nelson CJ, Mulhall JP. Predicting biochemical response to clomiphene citrate in men with hypogonadism. J Sex Med. 2014 Sep;11(9):2302-7. doi: 10.1111/jsm.12592. Epub 2014 Jun 5. — View Citation

Mikkelson TJ, Kroboth PD, Cameron WJ, Dittert LW, Chungi V, Manberg PJ. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril. 1986 Sep;46(3):392-6. doi: 10.1016/s0015-0282(16)49574-9. — View Citation

Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012 Nov;110(10):1524-8. doi: 10.1111/j.1464-410X.2012.10968.x. Epub 2012 Mar 28. — View Citation

Mulhall JP, Trost LW, Brannigan RE, Kurtz EG, Redmon JB, Chiles KA, Lightner DJ, Miner MM, Murad MH, Nelson CJ, Platz EA, Ramanathan LV, Lewis RW. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018 Aug;200(2):423-432. doi: 10.1016/j.juro.2018.03.115. Epub 2018 Mar 28. — View Citation

Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006 Jul;60(7):762-9. doi: 10.1111/j.1742-1241.2006.00992.x. — View Citation

Murdter TE, Kerb R, Turpeinen M, Schroth W, Ganchev B, Bohmer GM, Igel S, Schaeffeler E, Zanger U, Brauch H, Schwab M. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet. 2012 Mar 1;21(5):1145-54. doi: 10.1093/hmg/ddr543. Epub 2011 Nov 22. — View Citation

Pasqualotto FF, Fonseca GP, Pasqualotto EB. Azoospermia after treatment with clomiphene citrate in patients with oligospermia. Fertil Steril. 2008 Nov;90(5):2014.e11-2. doi: 10.1016/j.fertnstert.2008.03.036. Epub 2008 Jun 16. — View Citation

Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. Testosterone supplementation versus clomiphene citrate for hypogonadism: an age matched comparison of satisfaction and efficacy. J Urol. 2014 Sep;192(3):875-9. doi: 10.1016/j.juro.2014.03.089. Epub 2014 Mar 21. — View Citation

Tenover JS, Bremner WJ. The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. J Androl. 1991 Jul-Aug;12(4):258-63. — View Citation

Wheeler KM, Sharma D, Kavoussi PK, Smith RP, Costabile R. Clomiphene Citrate for the Treatment of Hypogonadism. Sex Med Rev. 2019 Apr;7(2):272-276. doi: 10.1016/j.sxmr.2018.10.001. Epub 2018 Dec 3. — View Citation

Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, Rosner M, Dwyer A, Podolski J. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics. BJU Int. 2013 Jul 12;112(8):1188-200. doi: 10.1111/bju.12363. Online ahead of print. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in serum testosterone	Change in serum testosterone	Evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.
Secondary	Change in FSH levels	Serum levels of follicle-stimulating hormone (FSH)	Evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.
Secondary	Change in LH levels	Serum levels of luteinizing hormone (LH)	Evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.
Secondary	Change in estradiol levels	Serum levels of estradiol levels	Evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.