Clinical trial NCT04523480: Testopel ® vs. Generic Testosterone Pellets.
Official title: Randomized Control Trial of Long Acting Subcutaneous Testosterone Pellets for Hypogonadism: Testopel ® vs. Generic Testosterone Pellets.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypogonadism
Keywords: Low T
Low Testosterone
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Empower Research Inc
First posted: 2020-08-21
Enrollment: 75
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate changes in vascular parameters in subjects receiving Testopel 75mg (one time) versus subjects receiving Compounded Testosterone pellets 100mg (one time) versus subjects receiving Compounded Testosterone pellets 200mg (one time) to participant with clinical hypogonadism.

Detailed description: Hypogonadism, or low testosterone (Low T), is the deficiency in producing testosterone by the testes. Testosterone pellets is a long-acting formulation of Testosterone Replacement Therapy (TRT) that is delivered subcutaneously to men diagnosed with low T. Advantages to subcutaneous testosterone pellets include ease of delivery and decreased risk of the medication being transfer upon skin contact to woman or children. Long acting testosterone replacement Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month post-implantation and sustained therapeutic levels (\>300) for 4-6 months.

Participants will be randomly assigned to 1 of 3 study groups. In one of the groups the treatment will include implantation of Testopel ® 750mg (10 pellets with 75mg pellet) one time, in the second group, treatment will include compounded subcutaneous testosterone 800mg (8 pellets with 100mg pellet) one time and in the third group, treatment will include compounded subcutaneous testosterone 800mg (4 pellets with 200mg pellet) one time.

The treatment takes approximately 30 minutes and will include: Clean and numb the insertion site with lidocaine at 1%, followed by small incision in the skin, implantation of pellets into subdermal fat layer and sealing the incision with Steri-strip. This is the current standard of care of Testopel insertion and same procedure will be followed with both compounded and commercial pellets.

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.
* Male between 18 and 75 years of age.
* 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 weeks following androgen treatment.
* 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, 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) or International Prostate Symptom Score (I-PSS) score \> 19 points.
* 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
  2. Hematocrit \< 35% or \> 50%
  3. 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 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.

Primary outcomes:
measure: Change in Testosterone (T) Levels
timeFrame: Baseline, 2 months, 4 months, and 6 months
Secondary outcomes:
measure: Change in Hematocrit (Hct) Levels.
timeFrame: Baseline, 2 months, 4 months, and 6 months
measure: Change in PSA Levels
timeFrame: Baseline, 2 months, 4 months, and 6 months
measure: Change in Estradiol Levels
timeFrame: Baseline, 2 months, 4 months, and 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami, Department of Urology
state: Florida
Study officials:
affiliation: University of Miami
name: Ranjith Ramasamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Walker WH. Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis. 2011 Apr;1(2):116-120. doi: 10.4161/spmg.1.2.16956.
citation: 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.
citation: 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-.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.