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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04439799
Recruitment Status : Recruiting
First Posted : June 19, 2020
Last Update Posted : August 11, 2020
Sponsor:
Collaborator:
Acerus Pharmaceuticals Corporation
Information provided by (Responsible Party):
Ranjith Ramasamy, MD, University of Miami

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.

Condition or disease Intervention/treatment Phase
Hypogonadism, Male Drug: Testosterone Cypionate 200 MG/ML Drug: Intranasal Testosterone Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 7, 2020
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : June 15, 2022


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 Name: Natesto




Primary Outcome Measures :
  1. Change in Hematocrit (Hct) levels. [ Time Frame: Baseline, 4 months ]
    Changes in serum Hct levels will be assessed in %


Secondary Outcome Measures :
  1. Change in gonadotropin levels [ Time Frame: Baseline, 4 months ]
    Change in serum gonadotropin levels including Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), both assessed in mIU/mL.

  2. Change in hormone levels [ Time Frame: Baseline, 4 months ]
    Change in serum hormone levels including Testosterone, 17 -Hydroxyprogesterone (17-OHP) and Dihydrotestosterone (DHT), all assessed in ng/dL.

  3. Change in PSA levels [ Time Frame: Baseline, 4 months ]
    Change in serum Prostate Specific Antigen (PSA) levels will be assessed in ng/mL.

  4. Change in estrogen levels [ Time Frame: Baseline, 4 months ]
    Change in serum estrogen levels will be assessed in pg/mL.

  5. Change in Testicular Volume [ Time Frame: baseline, 4 months ]
    changes in testicular volume will be assessed in cc. An orchidometer will be the instrument of assessment during physical exam.

  6. Changes in IIEF score [ Time Frame: Baseline, 4 months ]
    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.

  7. 8. Change in SF-15 Erectile Function Domain Scores [ Time Frame: Baseline, 4 months ]
    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.

  8. Change in SF-15 Intercourse Satisfaction Domain Scores [ Time Frame: Baseline, 4 months ]
    The SF-15 Questionnaire Intercourse Satisfaction domain has a total score ranging from 0-15 with the higher score indicating better intercourse satisfaction.

  9. Change in SF-15 Questionnaire Scores [ Time Frame: Baseline, 4 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 HCT 48%
    2. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04439799


Contacts
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Contact: Manuel Molina, MD 3052434873 m.molina.leyba@miami.edu

Locations
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United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Ranjith Ramasamy, MD    305-243-4562    ramasamy@miami.edu   
Principal Investigator: Ranjith Ramasamy, MD         
Sponsors and Collaborators
University of Miami
Acerus Pharmaceuticals Corporation
Investigators
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Principal Investigator: Ranjith Ramasamy, MD University of Miami
Publications:

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Responsible Party: Ranjith Ramasamy, MD, Director of Male Fertility and Andrology, University of Miami, University of Miami
ClinicalTrials.gov Identifier: NCT04439799    
Other Study ID Numbers: 20200201
First Posted: June 19, 2020    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Ranjith Ramasamy, MD, University of Miami:
Low T
Additional relevant MeSH terms:
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Hypogonadism
Eunuchism
Gonadal Disorders
Endocrine System Diseases
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents