CompletedNCT03203681Updated Oct 19, 2021Results posted

Natesto Effects on Testosterone, Luteinizing Hormone, Follicle Stimulating Hormone and Semen Parameters

A Phase 4 interventional study of Natesto in Hypogonadism, Male, sponsored by University of Miami. Completed at 1 site in United States. Open to male participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2021-10-19.

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

Phase: Phase 4
Study type: Interventional
Enrollment: 60
Allocation: Not applicable
Ages: 18 Years to 55 Years
Sex: Male

Study summary

Low testosterone affects more than 10% of men worldwide, with high incidence in the elderly.This will be a prospective case study. The investigators will identify men with hypogonadism in our clinic interested in Natesto for testosterone replacement therapy (TRT). Natesto is a relatively new form of testosterone replacement therapy that is delivered intranasal to men diagnosed with low testosterone. Current advantages to Natesto include ease of delivery and decreased risk of transference. Recently Natesto 4.5% (125 uL/nostril, 11.0mg testosterone/dose), three times a day (TID) dosing was shown to also increase serum testosterone while maintaining normal, though decreased, serum levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone(FSH). 40 participants will be enrolled and receive treatment with Natesto.The study will identify men with confirmed hypogonadism (testosterone (T) \<350 on 2 consecutive Testosterone samples collected greater than 1.5 hours apart between 6am and 10am with demonstrated symptoms of hypogonadism). Participants with a history of prostate cancer, testis cancer, azoospermia, or genetic cause of hypogonadism will be excluded.

Read the detailed description

Low testosterone affects more than 10% of men worldwide, with high incidence in the elderly). While Natesto has been shown to have positive effects on Testosterone while maintaining LH and FSH, the impact on sperm count has not yet been proven.

Study Design and Duration of Treatment: Participants will take Natesto 11g intra nasally there times a day (TID) for 16 weeks (120 days) between serum and semen evaluations.

Subject Population: The study will identify men with confirmed hypogonadism (testosterone (T) \<350 on 2 consecutive Testosterone samples collected greater than 1.5 hours apart between 6am and 10am with demonstrated symptoms of hypogonadism). Subjects with a history of prostate cancer, testis cancer, azoospermia, or genetic cause of hypogonadism will be excluded.

Number of subjects: 40 participants will be enrolled and receive treatment with Natesto.

Study Duration:Total participation in the study will be approximately 24-28 weeks.

Study Procedures: Participants will undergo a total of six study visits. At the first visit, subjects will undergo screening procedures which will include signing of the consent form, physical exam, assessment for inclusion and exclusion criteria, Sexual Health Inventory in Men (SHIM) and quality of life questionnaire, blood sample for clinical laboratory assessment, and a semen analysis. At visit 2, subjects will undergo a second semen analysis and blood analysis for T. After 12 weeks (90 days), Participants will return for a third visit for blood sample and semen analysis as well as safety monitoring. The Participants will also be given SHIM and quality of life questionnaires. This procedure will be repeated at week 24 to get a final blood and semen analysis.

Study Endpoints: The primary endpoint will be change in FSH, LH, Estradiol, T, and Semen Analysis after 12 weeks and 24 weeks of treatment with Natesto. The secondary endpoint will be monitoring for adverse events

Statistical Methods: Analyses will consist of summaries of the values and total change from baseline in each value (visit value versus baseline value) using descriptive statistics (sample size, mean, median, standard deviation, 95% confidence interval, minimum, and maximum). The change from baseline in each endpoint will compared using a two-sample t-test, or the Wilcoxon rank sum test if distributional assumptions are violated. The primary time point of interest for assessing hormone effects is the week 12 visit.

Conditions studied

Hypogonadism, Male

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Who can participate

Ages eligible: 18 Years to 55 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.
Male between 18 and 55 years of age, inclusive, with documented onset of hypogonadism prior to age 55.
Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).
Serum total testosterone \< 350 ng/dL based on 2 consecutive blood samples obtained at least 1.5 hours apart between 6:00 am and 10:00 am following an appropriate washout of current androgen replacement therapy.
Naïve to androgen replacement or has discontinued current treatment and completed a washout of 4 weeks following androgen treatment (excluding Testopel). Washout must be completed prior to collection of baseline serum testosterone samples to determine study eligibility.
Judged to be in good general health as determined by the principal investigator based upon 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, castor oil or product excipients.
Clinically significant findings in the prestudy examinations including abnormal breast examination requiring follow-up, abnormal ECG.
Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) or International Prostate Symptoms Score (I-PSS) > 19 points.
Body mass index (BMI) ≥ 30 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 \< 11.5 g/dL or > 16 g/dL
2. Hematocrit \< 35% or > 54%
3. Serum transaminases > 2.5 times upper limit of normal
4. Serum bilirubin > 2.0 mg/dL
5. Creatinine > 2.0 mg/dL f. Prostate-Specific Antigen (PSA) > 2 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 investigational product within 4 weeks or within 5 half-lives prior to the start of treatment.
Inability to understand and provide written informed consent for the study.
Considered by the investigator or the sponsor-designated physician, for any reason, that the subject is an unsuitable candidate to receive Natesto.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 60 participants (actual)

Study arms

Other
Natesto
Participants in this group will receive Natesto for a 24 consecutive weeks treatment course.
Drug: Natesto

Interventions

DrugNatesto
4.5% nasal testosterone. 11.0 mg testosterone administered per dose (2 pump actuations, 1 pump per nostril) applied intranasally three times a day.

What researchers measure

Primary outcomes

Change in Testosterone Levels From Baseline to 27 Weeks
Testosterone levels measured in ng/dL analyzed from peripheral venous puncture blood draw
Time frame: Baseline, 27 Weeks
Change in Estradiol Levels From Baseline to 27 Weeks
Estradiol levels measured in pg/mL analyzed from peripheral venous puncture blood draw
Time frame: Baseline, 27 Weeks
Change in Gonadotropin Levels From Baseline to 27 Weeks
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) levels, both measured in mIU/mL analyzed from peripheral venous puncture blood draw
Time frame: Baseline, 27 Weeks
Number of Participants With an Increase in SF-36 QOL Scores From Baseline
The number of participants with an increase of at least 1 point from their SF-36 QOL scores from baseline will be reported. Short Form-36 (SF-36) Quality of Life (QOL) questionnaire has a proprietary scoring system that ranges from 1-5 and each domain is individually assessed
Time frame: 27 Weeks
Change in Sperm Counts From Baseline to 27 Weeks
Sperm count measured in million sperm/mL analyzed from semen sample
Time frame: Baseline, 27 Weeks
Incidence of Adverse Events
Incidence of adverse events as assessed per treating physician
Time frame: 27 Weeks

Results

Posted Aug 23, 2021

Participant flow

Participant flow — Overall Study
Milestone	Natesto
Started	60
3 month	44
6 months	33
Completed	33
Not completed	27

Outcome measures

PrimaryChange in Testosterone Levels From Baseline to 27 Weeks

Testosterone levels measured in ng/dL analyzed from peripheral venous puncture blood draw

Time frame:: Baseline, 27 Weeks
Reported as:: Mean · ng/dL

Change in Testosterone Levels From Baseline to 27 Weeks
ng/dL	Natesto
Change in Testosterone Levels From Baseline to 27 Weeks	652 ± 305

PrimaryChange in Estradiol Levels From Baseline to 27 Weeks

Estradiol levels measured in pg/mL analyzed from peripheral venous puncture blood draw

Time frame:: Baseline, 27 Weeks
Reported as:: Mean · pg/mL

Change in Estradiol Levels From Baseline to 27 Weeks
pg/mL	Natesto
Change in Estradiol Levels From Baseline to 27 Weeks	21.6 ± 14

PrimaryChange in Gonadotropin Levels From Baseline to 27 Weeks

Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) levels, both measured in mIU/mL analyzed from peripheral venous puncture blood draw

Time frame:: Baseline, 27 Weeks
Reported as:: Mean · mIU/mL

Change in Gonadotropin Levels From Baseline to 27 Weeks
mIU/mL	Natesto
Follicle Stimulating Hormone	3.0 ± 2.9
Luteinizing Hormone	2.6 ± 3.1

PrimaryNumber of Participants With an Increase in SF-36 QOL Scores From Baseline

The number of participants with an increase of at least 1 point from their SF-36 QOL scores from baseline will be reported. Short Form-36 (SF-36) Quality of Life (QOL) questionnaire has a proprietary scoring system that ranges from 1-5 and each domain is individually assessed

Time frame:: 27 Weeks
Reported as:: Count of participants · Participants

Number of Participants With an Increase in SF-36 QOL Scores From Baseline
Participants	Natesto
Number of Participants With an Increase in SF-36 QOL Scores From Baseline	32

PrimaryChange in Sperm Counts From Baseline to 27 Weeks

Sperm count measured in million sperm/mL analyzed from semen sample

Time frame:: Baseline, 27 Weeks
Reported as:: Mean · million sperm/mL

Change in Sperm Counts From Baseline to 27 Weeks
million sperm/mL	Natesto
Change in Sperm Counts From Baseline to 27 Weeks	33.9 ± 24.3

PrimaryIncidence of Adverse Events

Incidence of adverse events as assessed per treating physician

Time frame:: 27 Weeks
Reported as:: Count of participants · Participants

Incidence of Adverse Events
Participants	Natesto
Azoospermia	1
Severe Oligospermia	3
Nasal irritation	5
sinusitis	1
epistaxis	1

Adverse events

Collected over 28 weeks. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Natesto	0/60 (0%)	4/60 (6.7%)	5/60 (8.3%)

Most frequent serious events

Most frequent serious events
Event	Natesto
Severe OligospermiaReproductive system and breast disorders	3/60
AzoospermiaReproductive system and breast disorders	1/60

Most frequent other events

Most frequent other events
Event	Natesto
Nasal IrritationInjury, poisoning and procedural complications	5/60
SinusitisGeneral disorders	1/60
EpistaxisGeneral disorders	1/60

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Natesto
<=18 years	0
Between 18 and 65 years	60
>=65 years	0

Sex: Female, Male
Sex: Female, Male(Participants)	Natesto
Female	0
Male	60

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Natesto
Demographics — Caucasian	12
Demographics — Black	2
Demographics — Hispanic	34
Demographics — Asian	1
Demographics — Other	11

Study locations

1 site

University of Miami
Miami, Florida 33136, United States

References and documents

Publications

Amory JK, Anawalt BD, Blaskovich PD, Gilchriest J, Nuwayser ES, Matsumoto AM. Testosterone release from a subcutaneous, biodegradable microcapsule formulation (Viatrel) in hypogonadal men. J Androl. 2002 Jan-Feb;23(1):84-91. doi: 10.1002/jand.2002.23.1.84. PubMed 11780927 ↗
Haring R, Ittermann T, Volzke H, Krebs A, Zygmunt M, Felix SB, Grabe HJ, Nauck M, Wallaschofski H. Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania. Aging Male. 2010 Dec;13(4):247-57. doi: 10.3109/13685538.2010.487553. Epub 2010 May 26. PubMed 20504090 ↗
Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. 2016 Apr;117(4):677-85. doi: 10.1111/bju.13337. Epub 2015 Oct 23. PubMed 26496621 ↗
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 ↗
Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med. 2004 Jan 29;350(5):482-92. doi: 10.1056/NEJMra022251. No abstract available. PubMed 14749457 ↗
Rogol AD, Tkachenko N, Bryson N. Natesto , a novel testosterone nasal gel, normalizes androgen levels in hypogonadal men. Andrology. 2016 Jan;4(1):46-54. doi: 10.1111/andr.12137. Epub 2015 Dec 22. Erratum In: Andrology. 2017 Jul;5(4):844. doi: 10.1111/andr.12402. PubMed 26695758 ↗

Study documents

Protocol and statistical analysis plan · Jul 9, 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: NCT03203681
Lead sponsor: University of Miami
Collaborators: Acerus Pharmaceuticals Corporation
Responsible party: Ranjith Ramasamy, MD (Director of Male Reproductive Medicine and Surgery/Assistant professor in Department of Urology at University of Miami, University of Miami) — Principal investigator
First posted: Jun 29, 2017
Start date: Oct 27, 2017
Primary completion: Jun 1, 2020
Completion: Jun 1, 2020
Results posted: Aug 23, 2021
Last update: Oct 19, 2021

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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