A Comparison of Side Effects in Hypogonadal Men Treated With Natesto Versus Testosterone Injections

Hypogonadism, Male Clinical Trial

Official title:

A Comparison of Side Effects in Hypogonadal Men Treated With Natesto Versus Testosterone Injections: A Phase IV, Prospective, Randomized, Non-Blinded, Multi-Institutional Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04439799
• Other study ID #: 20200201
• Status: Completed
• Phase: Phase 4
• Start date: August 7, 2020
• Est. completion date: February 9, 2023

Study information

• Verified date: November 2023
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate changes in vascular parameters and the prevalence of side effects in subjects receiving 1 cc (200mg) every 2 weeks intramuscular (IM) of Testosterone Cypionate versus subjects receiving 11mg three times daily (TID) Natesto to participant with clinical hypogonadism.

Description:

Administration of exogenous testosterone as efficacious treatment for male hypogonadism has been part of medical practice for more than 50 years. Testosterone replacement therapy (TRT) is becoming more widely available and has seen a greater than three-fold increase in use in men 40 years and older. Current delivery systems of TRT include transdermal gels and patches, intranasal gels (currently marketed as Natesto), injection therapy, and long acting subcutaneous pellets.

Natesto is a short-acting formulation of testosterone delivered intranasally to men diagnosed with low T. This has the potential to avoid side effects related to TRT that are commonly seen with other delivery methods, namely polycythemia, acne, male-pattern hair loss, azoospermia and hyperestrogenemia.

Testosterone Cypionate injections are the most common form of TRT in the USA. Testosterone Cypionate has many reported side effects, the most common being polycythemia, gynecomastia, hair loss, acne, decreased spermatogenesis, and testicular atrophy. In a multicenter retrospective study, it has been shown that the prevalence of polycythemia in men on testosterone replacement (injections) was 11.2%. In this study, we will compare hematocrit changes caused by treatment with Testosterone Cypionate and Natesto in a parallel arm, randomized study. To date, there have been no direct head-to-haed comparisons of these formulations.

We hypothesize that the short-acting pharmacokinetics of Natesto more closely resembles the natural pulsatility of testosterone and therefore can avoid side effects traditionally seen in long-acting, exogenous testosterone formulations

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: February 9, 2023
• Est. primary completion date: February 9, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Voluntarily sign and date the study consent form(s), which have been approved by an Institutional Review Board (IRB). Written consent must be obtained prior to the initiation of any study procedures.

2. Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).

3. Serum total testosterone < 300 ng/dL on 2 measurements

4. Naïve to androgen replacement or has discontinued current treatment and completed a washout of 4 months following androgen treatment.

5. Men deemed to be candidates for TRT based on the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG).

Exclusion Criteria:

1. History of significant sensitivity or allergy to androgens, or product excipients.

2. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up, abnormal ECG.

3. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s)

4. Body mass index (BMI) = 40 kg/m2.

5. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:

1. Baseline hemoglobin > 16 g/dL or Hematocrit (HCT) 48%

2. Prostate Specific Antigen (PSA) > 4 ng/mL

6. History of seizures or convulsions, including febrile, alcohol or drug withdrawal seizures.

7. History of any clinically significant illness, infection, or surgical procedure within 4 weeks prior to study drug administration.

8. History of stroke or myocardial infarction within the past 5 years.

9. History of, or current or suspected, prostate or breast cancer.

10. History of diagnosed, severe, untreated, obstructive sleep apnea.

11. History of abuse of alcohol or any drug substance in the opinion of the investigator within the previous 2 years.

12. Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 12 weeks prior to the start of treatment.

13. Inadequate venous access for collection of serial blood samples required for pharmacokinetic profiles.

14. Receipt of any subcutaneous testosterone pellets within the last 6 months.

15. Inability to understand and provide written informed consent for the study.

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadism, Male

Intervention

Drug:
• Testosterone Cypionate 200 Mg/ML
Participants in this group will receive intramuscular testosterone cypionate injections of 1 cc (200mg) once every 14 days for four months.
• Intranasal Testosterone
Participant in this group will receive Intranasal testosterone administered using a multi-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose) for 4 consecutive months,

Locations

Country	Name	City	State
United States	University of Miami Miller School of Medicine	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	Acerus Pharmaceuticals Corporation

Country where clinical trial is conducted

United States, 

References & Publications (11)

Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013 Aug 12;173(15):1465-6. doi: 10.1001/jamainternmed.2013.6895. No abstract available. Erratum In: JAMA Intern Med. 2013 Aug 12;173(15):1477. — View Citation

Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf). 1994 Mar;40(3):341-9. doi: 10.1111/j.1365-2265.1994.tb03929.x. — View Citation

Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab. 2013 Aug;27(4):557-79. doi: 10.1016/j.beem.2013.05.002. Epub 2013 Jul 5. — View Citation

Davidson JM, Camargo CA, Smith ER. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab. 1979 Jun;48(6):955-8. doi: 10.1210/jcem-48-6-955. — View Citation

Finkelstein JS, Klibanski A, Neer RM, Greenspan SL, Rosenthal DI, Crowley WF Jr. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med. 1987 Mar;106(3):354-61. doi: 10.7326/0003-4819-106-3-. — View Citation

Haring R, Volzke H, Steveling A, Krebs A, Felix SB, Schofl C, Dorr M, Nauck M, Wallaschofski H. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J. 2010 Jun;31(12):1494-501. doi: 10.1093/eurheartj/ehq009. Epub 2010 Feb 17. — View Citation

Jockenhovel F, Vogel E, Reinhardt W, Reinwein D. Effects of various modes of androgen substitution therapy on erythropoiesis. Eur J Med Res. 1997 Jul 28;2(7):293-8. — View Citation

Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65. doi: 10.1210/jcem.81.12.8954042. — View Citation

Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000 Aug;85(8):2670-7. doi: 10.1210/jcem.85.8.6731. — View Citation

Ullah MI, Riche DM, Koch CA. Transdermal testosterone replacement therapy in men. Drug Des Devel Ther. 2014 Jan 9;8:101-12. doi: 10.2147/DDDT.S43475. eCollection 2014. — View Citation

Walker WH. Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis. 2011 Apr;1(2):116-120. doi: 10.4161/spmg.1.2.16956. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hematocrit (Hct) Levels.	Changes in serum Hematocrit levels will be assessed in percentage	Baseline to 4 months
Secondary	Change in Hormone Levels	Change in serum hormone levels including Testosterone, 17-Hydroxyprogesterone (17-OHP) assessed in ng/dL.	Baseline to 4 months
Secondary	Change in PSA Levels	Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.	Baseline to 4 months
Secondary	Change in Estradiol Levels	Change in serum estradiol levels will be assessed in pg/mL.	Baseline to 4 months
Secondary	Changes in IIEF-6 Score	The International Index of Erectile Function (IIEF)-6 is a 6-item subdomain self-evaluation questionnaire of erectile function. Each item is scored from 0-5 with the total score ranging from 0-30 with the higher score indicating better erectile function.	Baseline to 4 months