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

NCT ID: NCT04439799

Last Updated: 2023-12-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-07

Study Completion Date

2023-02-09

Brief Summary

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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.

Detailed Description

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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

Conditions

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Hypogonadism, Male

Keywords

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Low T

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Testosterone Cypionate Group

Participants in this group will receive the intramuscular Testosterone Cypionate intervention for four months

Group Type ACTIVE_COMPARATOR

Testosterone Cypionate 200 Mg/ML

Intervention Type DRUG

Participants in this group will receive intramuscular testosterone cypionate injections of 1 cc (200mg) once every 14 days for four months.

Natesto Group

Participants in this group will receive the intranasal testosterone (Natesto) intervention for four months.

Group Type ACTIVE_COMPARATOR

Intranasal Testosterone

Intervention Type DRUG

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,

Interventions

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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.

Intervention Type DRUG

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,

Intervention Type DRUG

Other Intervention Names

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Natesto

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Acerus Pharmaceuticals Corporation

INDUSTRY

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Ranjith Ramasamy, MD

Director of Male Fertility and Andrology, University of Miami

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ranjith Ramasamy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 24054931 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20164245 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 22319659 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8954042 (View on PubMed)

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-.

Reference Type BACKGROUND
PMID: 3544993 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9233903 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7514512 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 447801 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10946864 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23939517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24470750 (View on PubMed)

Rivero MJ, Ory J, Diaz P, Thirumavalavan N, Han S, Reis IM, Ramasamy R. Comparison of Hematocrit Change in Testosterone-deficient Men Treated With Intranasal Testosterone Gel vs Intramuscular Testosterone Cypionate: A Randomized Clinical Trial. J Urol. 2023 Jul;210(1):162-170. doi: 10.1097/JU.0000000000003487. Epub 2023 May 1.

Reference Type DERIVED
PMID: 37126399 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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20200201

Identifier Type: -

Identifier Source: org_study_id