CompletedNCT04439799Updated Dec 13, 2023Results posted

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

A Phase 4 interventional study of Testosterone Cypionate 200 Mg/ML and Intranasal Testosterone in Hypogonadism, Male, sponsored by University of Miami. Completed at 1 site in United States. Open to male participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-12-13.

Sponsored by University of Miami · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 81
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: Male

Study 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.

Read the 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

Conditions studied

Hypogonadism, Male

Browse trials for

Keywords

Low T

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: Male
Accepts healthy volunteers: No

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

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 Hematocrit (HCT) 48%
2. Prostate Specific Antigen (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.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 81 participants (actual)

Study arms

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
Active comparator
Natesto Group
Participants in this group will receive the intranasal testosterone (Natesto) intervention for four months.
Drug: Intranasal Testosterone

Interventions

DrugTestosterone 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.
DrugIntranasal 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,
Also known as: Natesto

What researchers measure

Primary outcomes

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

Secondary outcomes

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

Results

Posted Dec 13, 2023

Participant flow

Participant flow — Overall Study
Milestone	Testosterone Cypionate Group	Natesto Group
Started	41	40
Completed	31	23
Not completed	10	17
Withdrew: Lost to follow-up	6	6
Withdrew: Withdrawal by subject	2	6
Withdrew: Adverse event	2	5

Outcome measures

PrimaryChange in Hematocrit (Hct) Levels.

Changes in serum Hematocrit levels will be assessed in percentage

Time frame:: Baseline to 4 months
Reported as:: Mean · percentage of hematocrit

Change in Hematocrit (Hct) Levels.
percentage of hematocrit	Testosterone Cypionate Group	Natesto Group
Change in Hematocrit (Hct) Levels.	3.0 (2.8 to 5)	-0.6 (-1.5 to 0.4)

SecondaryChange in Hormone Levels

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

Time frame:: Baseline to 4 months
Reported as:: Mean · ng/dL

Change in Hormone Levels
ng/dL	Testosterone Cypionate Group	Natesto Group
Testosterone	511 (373 to 650)	283 (149 to 417)
17-OHP	-39.8 (-53.1 to -26.5)	-8.8 (-24.4 to 6.7)

SecondaryChange in PSA Levels

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

Time frame:: Baseline to 4 months
Reported as:: Mean · ng/mL

Change in PSA Levels
ng/mL	Testosterone Cypionate Group	Natesto Group
Change in PSA Levels	0.6 (-0.02 to 1.23)	0.05 (-0.22 to 0.32)

SecondaryChange in Estradiol Levels

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

Time frame:: Baseline to 4 months
Reported as:: Mean · pg/mL

Change in Estradiol Levels
pg/mL	Testosterone Cypionate Group	Natesto Group
Change in Estradiol Levels	22.9 (11 to 34.8)	1.1 (-5.7 to 7.8)

SecondaryChanges 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.

Time frame:: Baseline to 4 months
Reported as:: Mean · score on a scale

Changes in IIEF-6 Score
score on a scale	Testosterone Cypionate Group	Natesto Group
Changes in IIEF-6 Score	4.8 (1.1 to 8.5)	0.2 (-3.6 to 4)

Adverse events

Collected over 4 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Testosterone Cypionate Group	0/41 (0%)	0/41 (0%)	2/41 (4.9%)
Natesto Group	0/40 (0%)	0/40 (0%)	5/40 (12.5%)

Most frequent other events

Most frequent other events
Event	Testosterone Cypionate Group	Natesto Group
Nasal CongestionRespiratory, thoracic and mediastinal disorders	0/41	3/40
LabyrithitisEar and labyrinth disorders	0/41	1/40
DyspneaRespiratory, thoracic and mediastinal disorders	0/41	1/40
Generalized EdemaGeneral disorders	1/41	0/40
AnemiaBlood and lymphatic system disorders	1/41	0/40

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Testosterone Cypionate Group	Natesto Group	Total
Mean	48.46 ± 11.86	48.2 ± 10.89	48.33 ± 11.32

Sex: Female, Male
Sex: Female, Male(Participants)	Testosterone Cypionate Group	Natesto Group	Total
Female	0	0	0
Male	41	40	81

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Testosterone Cypionate Group	Natesto Group	Total
Hispanic or Latino	29	22	51
Not Hispanic or Latino	12	18	30
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Testosterone Cypionate Group	Natesto Group	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	9	9
White	40	29	69
More than one race	0	0	0
Unknown or Not Reported	1	2	3

Study locations

1 site

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

References and documents

Publications

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. PubMed 24054931 ↗
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. PubMed 20164245 ↗
Walker WH. Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis. 2011 Apr;1(2):116-120. doi: 10.4161/spmg.1.2.16956. PubMed 22319659 ↗
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. PubMed 8954042 ↗
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-. PubMed 3544993 ↗
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. PubMed 9233903 ↗
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. PubMed 7514512 ↗
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. PubMed 447801 ↗
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. PubMed 10946864 ↗
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. PubMed 23939517 ↗
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. PubMed 24470750 ↗

Study documents

Protocol and statistical analysis plan · Feb 26, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT04439799
Lead sponsor: University of Miami
Collaborators: Acerus Pharmaceuticals Corporation
Responsible party: Ranjith Ramasamy, MD (Director of Male Fertility and Andrology, University of Miami, University of Miami) — Principal investigator
First posted: Jun 19, 2020
Start date: Aug 7, 2020
Primary completion: Feb 9, 2023
Completion: Feb 9, 2023
Results posted: Dec 13, 2023
Last update: Dec 13, 2023

Study contacts

Ranjith Ramasamy, MD

principal investigator · University of Miami

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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