Clinical trial NCT01446042: Safety and Efficacy of Intranasal TBS-1 Treatment of Male Hypogonadism
Official title: A 90-Day, Randomized, Dose-Ranging Study, Including Potential Dose Titration, Evaluating the Efficacy and Safety of Intranasal TBS-1 in the Treatment of Male Hypogonadism With Sequential Safety Extension Periods of 90 and 180 Days
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Male Hypogonadism
Lead sponsor: Acerus Pharmaceuticals Corporation
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 306
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
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 determine the efficacy (based on the pharmacokinetic profile of testosterone) and safety of TBS-1 in the treatment of hypogonadal men

Detailed description: This study is a 4 Period study consists of 16 visits with overnight clinic stays that span over year to help determine the efficacy of TBS-1 gel administered twice daily (b.i.d) and three times daily (t.i.d)

In addition, this study will investigate the safety and tolerability of TBS-1 after 90, 180 and 360 days of treatment.

Eligibility criteria: Inclusion Criteria

* Male between 18 and 80 years of age
* Able to understand and provide signed informed consent
* Have 2 fasting morning (0900 h ± 30 min) serum total testosterone levels \<300 ng/dL
* Body mass index between 18.5 kg/m2 and 35 kg/m2
* Hemoglobin level \> or = 13.0 g/dL
* Screening laboratory assessments within ±15% of the normal range, with the exception of liver function tests (which need to be within the normal range) and HbA1c (which must be \<7.0% \[9.5 mmol/L\]); lipid profile and endocrine profile assessments are also exempt from this range unless the assessments indicate a significant intercurrent illness other than testosterone deficiency
* Ear, nose and throat examination including nasal endoscopy without clinically significant abnormal findings
* Normal prostate for age based on digital rectal exam and a serum PSA \<4.0 ng/mL.

Exclusion Criteria

* Significant intercurrent disease of any type, in particular liver, kidney, heart disease, or psychiatric illness
* Hyperparathyroidism, uncontrolled diabetes mellitus, hypothyroidism, or hyperthyroidism (thyroid stimulating hormone should be \<1.5 times the upper limit of normal)
* Hematocrit \>54% at screening
* History of pituitary or hypothalamic tumors or history of malignancy within the past 5 years, excluding basal cell or squamous cell carcinoma of the skin curatively treated by surgery
* History of nasal surgery, specifically turbinoplasty, septoplasty, rhinoplasty, "nose job," or sinus surgery
* History of nasal fractures within the past 6 months and/or prior nasal fractures that caused a severely deviated anterior nasal septum
* Active allergies, such as rhinitis, rhinorrhea, and nasal congestion
* Mucosal inflammatory disorders, specifically pemphigus or Sjogren's syndrome
* Sinus disease, specifically acute sinusitis, chronic sinusitis, or allergic fungal sinusitis
* History of nasal disorders (eg, polyposis, recurrent epistaxis \[\>1 nose bleed per month\], abuse of nasal decongestants) or sleep apnea
* Use of any form of intranasal medication delivery, specifically nasal corticosteroids and oxymetazoline-containing nasal sprays (eg, Dristan® 12-Hour Nasal Spray)
* History of severe adverse drug reaction or leukopenia
* A known hypersensitivity to lidocaine or any materials that may be used during the study
* History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation
* History of hepatitis B, a positive test for hepatitis B surface antigen, a history of hepatitis C, or a positive test for hepatitis C antibody
* Presence of human immunodeficiency virus infection or antibodies
* History of asthma and ongoing asthma treatment
* History of sleeping problems or a shift worker
* Smoker of \>10 cigarettes (or equivalent) per day
* Regular consumption of more than 4 units of alcohol daily (1 unit is defined as 300 mL of beer, 1 glass of wine, or 1 measure of spirit) or difficulty abstaining from alcohol during the 48 hours prior to the 24 hour blood sampling visits
* History or current evidence of abuse of alcohol or any drug substance, licit or illicit, or positive urine drug and alcohol screen
* Treatment with androgen therapy within at least 2 weeks prior to baseline evaluations (subjects on androgen therapy will require a washout period of 4 weeks for depot products administered intramuscularly \[eg, testosterone enanthate 200 mg/mL\] and 2 weeks for products administered orally or topically \[oral, patch, gel, or buccal\])
* Current treatment with other androgens (eg, dehydroepiandrosterone \[DHEA\]), anabolic steroids, or other sex hormones
* Treatment with estrogens, gonadotropin-releasing hormone (GnRH) agonists, or growth hormone within previous 12 months
* Treatment with drugs that interfere with the metabolism of testosterone, such as anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole, spironolactone, or testolactone
* Treatment with any antihypertensive, antidepressant, tranquilizer, or histamine 2 (H2) receptor blocker that is not part of a stable regimen (stable dose for at least 3 months prior to baseline);
* Poor compliance history or low likelihood of maintaining attendance
* Participation in any other research study during the conduct of this study or 30 days prior to the initiation of this study or blood donation at any time during this study and within the 12 week period prior to screening

Primary outcomes:
measure: Serum Testosterone Cavg
timeFrame: 90 days
Secondary outcomes:
measure: Patients With a Certain Serum Total Testosterone Maximum Concentration on Day 90
timeFrame: 90 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics LLC
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center, Inc.
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Tucson
country: United States
facility: Quality of Life Medical Research Center
state: Arizona
city: Garden Grove
country: United States
facility: SC Clinical Research Inc
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Reseach Inc.
state: California
city: Clearwater
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic
state: Florida
city: Oviedo
country: United States
facility: Compass Research East LLC
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associates
state: Kentucky
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research LLC
state: Kentucky
city: Shreveport
country: United States
facility: Regional Urology LLC
state: Louisiana
city: Kansas City
country: United States
facility: Center for Pharmaceutical Research
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center Inc
state: South Carolina
city: Austin
country: United States
facility: Austin Center for Clinical Research
state: Texas
city: Dallas
country: United States
facility: Reseach Across America
state: Texas
city: Houston
country: United States
facility: Centex Research
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: San Antonio
country: United States
facility: Cetero Research
state: Texas
city: West Valley City
country: United States
facility: Granger Medical Clinic
state: Utah
city: Norfolk
country: United States
facility: National Clinical Research - Norfolk
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research
state: Virginia
city: Olympia
country: United States
facility: Capital Clinical Reseach Center
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
Study officials:
affiliation: Trimel Pharmaceuticals Corporation
name: Natalia Tkachenko, MD
role: STUDY_DIRECTOR
References:
citation: 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.