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

NCT ID: NCT03203681

Last Updated: 2021-10-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-27

Study Completion Date

2020-06-01

Brief Summary

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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.

Detailed Description

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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

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Hypogonadism, Male

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Natesto

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

Group Type OTHER

Natesto

Intervention Type DRUG

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

Interventions

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Natesto

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

Intervention Type DRUG

Eligibility Criteria

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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

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Acerus Pharmaceuticals Corporation

INDUSTRY

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Ranjith Ramasamy, MD

Director of Male Reproductive Medicine and Surgery/Assistant professor in Department of Urology at University of Miami

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ranjith Ramasamy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of Miami

Miami, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 11780927 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20504090 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26496621 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24470750 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14749457 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26695758 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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20170462

Identifier Type: -

Identifier Source: org_study_id