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

November 21, 2023 updated by: Ranjith Ramasamy, MD, University of Miami

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Testosterone Cypionate Group
Participants in this group will receive the intramuscular Testosterone Cypionate intervention for four months
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.
Active Comparator: Natesto Group
Participants in this group will receive the intranasal testosterone (Natesto) intervention for four months.
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,
Other Names:
  • Natesto

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hematocrit (Hct) Levels.
Time Frame: Baseline to 4 months
Changes in serum Hematocrit levels will be assessed in percentage
Baseline to 4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hormone Levels
Time Frame: Baseline to 4 months
Change in serum hormone levels including Testosterone, 17-Hydroxyprogesterone (17-OHP) assessed in ng/dL.
Baseline to 4 months
Change in PSA Levels
Time Frame: Baseline to 4 months
Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.
Baseline to 4 months
Change in Estradiol Levels
Time Frame: Baseline to 4 months
Change in serum estradiol levels will be assessed in pg/mL.
Baseline to 4 months
Changes in IIEF-6 Score
Time Frame: Baseline to 4 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Collaborators

Acerus Pharmaceuticals Corporation

Investigators

  • Principal Investigator: Ranjith Ramasamy, MD, University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2020

Primary Completion (Actual)

February 9, 2023

Study Completion (Actual)

February 9, 2023

Study Registration Dates

First Submitted

May 25, 2020

First Submitted That Met QC Criteria

June 18, 2020

First Posted (Actual)

June 19, 2020

Study Record Updates

Last Update Posted (Estimated)

December 13, 2023

Last Update Submitted That Met QC Criteria

November 21, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20200201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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