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

Primary Purpose

Hypogonadism, Male

Status

Active

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Testosterone Cypionate 200 MG/ML

Intranasal Testosterone

About this trial

This is an interventional treatment trial for Hypogonadism, Male focused on measuring Low T

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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.
Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).
Serum total testosterone < 300 ng/dL on 2 measurements
Naïve to androgen replacement or has discontinued current treatment and completed a washout of 4 months following androgen treatment.
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:

History of significant sensitivity or allergy to androgens, or product excipients.
Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up, abnormal ECG.
Abnormal prostate digital rectal examination (DRE) with palpable nodule(s)
Body mass index (BMI) ≥ 40 kg/m2.
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 HCT 48%
2. PSA > 4 ng/mL
History of seizures or convulsions, including febrile, alcohol or drug withdrawal seizures.
History of any clinically significant illness, infection, or surgical procedure within 4 weeks prior to study drug administration.
History of stroke or myocardial infarction within the past 5 years.
History of, or current or suspected, prostate or breast cancer.
History of diagnosed, severe, untreated, obstructive sleep apnea.
History of abuse of alcohol or any drug substance in the opinion of the investigator within the previous 2 years.
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.
Inadequate venous access for collection of serial blood samples required for pharmacokinetic profiles.
Receipt of any subcutaneous testosterone pellets within the last 6 months.
Inability to understand and provide written informed consent for the study.

Sites / Locations

University of Miami Miller School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Testosterone Cypionate Group

Natesto Group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in Hematocrit (Hct) levels.

Changes in serum Hct levels will be assessed in %

Secondary Outcome Measures

Change in gonadotropin levels

Change in serum gonadotropin levels including Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), both assessed in mIU/mL.

Change in hormone levels

Change in serum hormone levels including Testosterone, 17 -Hydroxyprogesterone (17-OHP) and Dihydrotestosterone (DHT), all assessed in ng/dL.

Change in PSA levels

Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.

Change in estrogen levels

Change in serum estrogen levels will be assessed in pg/mL.

Change in Testicular Volume

changes in testicular volume will be assessed in cc. An orchidometer will be the instrument of assessment during physical exam.

Changes in IIEF score

The International Index of Erectile Function (IIEF)-15 is a 5-item subdomain self-evaluation questionnaire of erectile function. Each item is scored from 0-5 with the total score ranging from 0-25 with the higher score indicating better erectile function.

8. Change in SF-15 Erectile Function Domain Scores

The Short Form (SF)-15 Questionnaire Erectile Function domain has a total score ranging from 0-25 with the higher score indicating better erectile function.

Change in SF-15 Intercourse Satisfaction Domain Scores

The SF-15 Questionnaire Intercourse Satisfaction domain has a total score ranging from 0-15 with the higher score indicating better intercourse satisfaction.

Change in SF-15 Questionnaire Scores

The SF-15 Questionnaire Orgasmic Function, Sexual Desire and Overall Satisfaction domains each has a total score ranging from 0-10 with the higher score indicating better outcomes.

Full Information

NCT ID

NCT04439799

First Posted

May 25, 2020

Last Updated

May 10, 2023

Sponsor

University of Miami

Collaborators

Acerus Pharmaceuticals Corporation

1. Study Identification

Unique Protocol Identification Number

NCT04439799

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 7, 2020 (Actual)

Primary Completion Date

December 15, 2023 (Anticipated)

Study Completion Date

June 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

Collaborators

Acerus Pharmaceuticals Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypogonadism, Male

Keywords

Low T

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Testosterone Cypionate Group

Arm Type

Active Comparator

Arm Description

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

Arm Title

Natesto Group

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Testosterone Cypionate 200 MG/ML

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Intranasal Testosterone

Other Intervention Name(s)

Natesto

Intervention Description

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,

Primary Outcome Measure Information:

Title

Change in Hematocrit (Hct) levels.

Description

Changes in serum Hct levels will be assessed in %

Time Frame

Baseline, 4 months

Secondary Outcome Measure Information:

Title

Change in gonadotropin levels

Description

Change in serum gonadotropin levels including Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), both assessed in mIU/mL.

Time Frame

Baseline, 4 months

Title

Change in hormone levels

Description

Change in serum hormone levels including Testosterone, 17 -Hydroxyprogesterone (17-OHP) and Dihydrotestosterone (DHT), all assessed in ng/dL.

Time Frame

Baseline, 4 months

Title

Change in PSA levels

Description

Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.

Time Frame

Baseline, 4 months

Title

Change in estrogen levels

Description

Change in serum estrogen levels will be assessed in pg/mL.

Time Frame

Baseline, 4 months

Title

Change in Testicular Volume

Description

changes in testicular volume will be assessed in cc. An orchidometer will be the instrument of assessment during physical exam.

Time Frame

baseline, 4 months

Title

Changes in IIEF score

Description

Time Frame

Baseline, 4 months

Title

8. Change in SF-15 Erectile Function Domain Scores

Description

The Short Form (SF)-15 Questionnaire Erectile Function domain has a total score ranging from 0-25 with the higher score indicating better erectile function.

Time Frame

Baseline, 4 months

Title

Change in SF-15 Intercourse Satisfaction Domain Scores

Description

The SF-15 Questionnaire Intercourse Satisfaction domain has a total score ranging from 0-15 with the higher score indicating better intercourse satisfaction.

Time Frame

Baseline, 4 months

Title

Change in SF-15 Questionnaire Scores

Description

The SF-15 Questionnaire Orgasmic Function, Sexual Desire and Overall Satisfaction domains each has a total score ranging from 0-10 with the higher score indicating better outcomes.

Time Frame

Baseline, 4 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). Serum total testosterone < 300 ng/dL on 2 measurements Naïve to androgen replacement or has discontinued current treatment and completed a washout of 4 months following androgen treatment. 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: History of significant sensitivity or allergy to androgens, or product excipients. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up, abnormal ECG. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) Body mass index (BMI) ≥ 40 kg/m2. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to: Baseline hemoglobin > 16 g/dL or HCT 48% PSA > 4 ng/mL History of seizures or convulsions, including febrile, alcohol or drug withdrawal seizures. History of any clinically significant illness, infection, or surgical procedure within 4 weeks prior to study drug administration. History of stroke or myocardial infarction within the past 5 years. History of, or current or suspected, prostate or breast cancer. History of diagnosed, severe, untreated, obstructive sleep apnea. History of abuse of alcohol or any drug substance in the opinion of the investigator within the previous 2 years. 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. Inadequate venous access for collection of serial blood samples required for pharmacokinetic profiles. Receipt of any subcutaneous testosterone pellets within the last 6 months. Inability to understand and provide written informed consent for the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ranjith Ramasamy, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami Miller School of Medicine

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24054931

Citation

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Citation

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PubMed Identifier

8954042

Citation

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

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