Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men (TU)

A Two-Arm, Open-Label, Randomized, Multi-Center Pharmacokinetic and Long-Term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men

To evaluate the pharmacokinetics of TU 750 mg and TU 1000 mg via multiple measurements of serum total testosterone.

Study Overview

• Status: Completed
• Conditions: Hypogonadism; Secondary Hypogonadism; Primary Hypogonadism
• Intervention / Treatment: Drug: Testosterone Undecanoate 750 mg; Drug: Testosterone Undecanoate 1000 mg

• Study Type: Interventional
• Enrollment (Actual): 531
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
      • Indevus Pharmaceuticals, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male with primary or secondary hypogonadism at least 18 years of age and for study part C2 weighs ≥143.3 lb (≥65 kg)
• Morning screening serum testosterone concentration <300 ng/dL

Exclusion Criteria:

• American Urological Association (AUA) Symptom Score ≥15 or significant prostatic symptoms
• History of carcinoma, tumors or induration of the prostate or the male mammary gland including suspicion thereof
• Screening serum prostate-specific antigen (PSA) level >4 ng/mL or hyperplasia of the prostate (size >75 cm3 as measured by transrectal ultrasonography)
• Past or present liver tumors or acute or chronic hepatic disease with impairment of liver function; liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) exceeding 1.5 times upper limit of normal
• History of deep vein thrombosis in the past 5 years or any history of cerebrovascular accident
• Severe acne
• Hypertension (systolic blood pressure >160 mm Hg and diastolic blood pressure >95 mm Hg) or coronary heart disease not stabilized by therapy as assessed by the investigator
• Insulin-dependent diabetes mellitus or uncontrolled non-insulin-dependent diabetes mellitus; patients with diabetes are excluded if screening glycated hemoglobin (HbA1C) level is >9%
• Use of any sex hormones within 28 days (for injectable testosterone preparations) or 7 days (for oral, gel, patch, etc, testosterone preparations) prior to screening visit and throughout the study (exclusive of administered study drug)
• Use of steroidal anabolic drugs or supplements (eg, dehydroepiandrosterone [DHEA]) by any application method within the 28 days prior to first administration of study drug and throughout the study (exclusive of administrated study drug)
• Medication with substances which might interfere with testosterone metabolism within 28 days before the first administration of study drug
• History of sleep apnea Insulin-dependent diabetes mellitus
• Use of steroidal anabolic drugs or supplements by any application method within the 28-days prior to the first administration of the study drug and throughout the study (exclusive of the administered study drug)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 750 mg dose of testosterone undecanoate	Drug: Testosterone Undecanoate 750 mg
Experimental: 2; 1000 mg dose testosterone undecanoate	Drug: Testosterone Undecanoate 1000 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 3rd Injection Interval in Part C	Responders were participants with serum total testosterone average concentration (Cavg) between 300 and 1000 ng/dL derived from the 3rd injection intensive pharmacokinetic (IPK) interval.	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Serum Total Testosterone Average Concentration During the 3rd Injection Interval in Part C	Serum total testosterone Cavg derived from the 3rd injection IPK interval	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Serum Total Testosterone Maximum Concentration During the 3rd Injection Interval in Part C	Serum total testosterone maximum concentration (Cmax) derived from the 3rd injection IPK interval	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 3rd Injection in Part C	Serum total testosterone concentration at the end of the dosing interval (Ctrough) derived from the 3rd injection IPK interval	Day 70 post injection at week 14
Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 4th Injection Interval in Part C	Responders were participants with serum total testosterone Cavg between 300 and 1000 ng/dL derived from the 4th injection IPK interval.	Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Serum Total Testosterone Average Concentration During the 4th Injection Interval in Part C	Serum total testosterone Cavg derived from the 4th injection IPK interval	Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Serum Total Testosterone Maximum Concentration During the 4th Injection Interval in Part C	Serum total testosterone Cmax derived from the 4th injection IPK interval	Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 4th Injection in Part C	Serum total testosterone Ctrough derived from the 4th injection IPK interval	Day 70 post injection at week 24
Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 2nd Injection Interval in Part C2	Success was defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL.	Days 0, 4, 7, 11, 14, and 70 post injection at week 4
Serum Total Testosterone Average Concentration During the 2nd Injection Interval in Part C2	Serum total testosterone Cavg derived from the 2nd injection IPK interval	Days 0, 4, 7, 11, 14, and 70 post injection at week 4
Serum Total Testosterone Maximum Concentration During the 2nd Injection Interval in Part C2	Serum total testosterone Cmax derived from the 2nd injection IPK interval	Days 0, 4, 7, 11, 14, and 70 post injection at week 4
Serum Total Testosterone at the End of the Dosing Interval Following the 2nd Injection in Part C2	Serum total testosterone Ctrough derived from the 2nd injection IPK interval	Day 70 post injection at week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Total Testosterone Maximum Concentration in Part A		Days 0, 4, 7, 11, 14, 21, 28, 42, 56, 70, and 84 post injection at week 1, week 12, week 24, and week 36; and post injection at weeks 48, 60, 72, 84, 96, 108, and 120
Serum Total Testosterone Maximum Concentration in Part B		Post injection at week 1; post injection at week 8; days 0, 4, 7, 11, 14, 21, 28, 42, 56, 70, and 84 post injection at week 20; and post injection at weeks 32, 44, 56, 68, and 80
Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 3rd Injection Interval in Part C	Success is defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL.	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Percentage of Participants With at Least 1 Serum Total Testosterone Level <300 ng/dL at Any Time During the 3rd Injection Interval in Part C		Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Percentage of Participants With Serum Total Testosterone Average Concentration ≥300 ng/dL During the 3rd Injection Interval in Part C		Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 3rd Injection Interval in Part C		Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Percentage of Participants With Clinical Success During the 3rd Injection Interval in Part C	Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Percentage of Participants With Serum Total Testosterone Maximum Concentration ≤1500, >1500 to <1800, 1800 to 2500, and >2500 ng/dL During the 3rd Injection Interval in Part C		Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14
Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 4th Injection Interval in Part C	Success is defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL.	Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Percentage of Participants With at Least 1 Serum Total Testosterone Level <300 ng/dL at Any Time During the 4th Injection Interval in Part C		Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Percentage of Participants With Average Serum Total Testosterone Concentration ≥300 ng/dL During the 4th Injection Interval in Part C		Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 4th Injection Interval in Part C		Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Percentage of Participants With Clinical Success During the 4th Injection Interval in Part C	Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL	Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Percentage of Participants With Serum Total Testosterone Maximum Concentration ≤1500, >1500 to <1800, 1800 to 2500, and >2500 ng/dL During the 4th Injection Interval in Part C		Days 0, 4, 7, 11, 42, and 70 post injection at week 24
Percentage of Participants by Collapsed Category for Each Parameter of the Male Patient Global Assessment (M-PGA) at Day 21 of the 3rd Injection Interval in Part C	M-PGA is a 5-item self-report questionnaire to assess perception of change from pretreatment or baseline in hypogonadal symptoms including confidence/self-esteem, sexual performance, moods/behavior, overall feeling of well-being, and satisfaction with study treatment rated on a 7-point scale where items 1-4 were rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7 (very much worse) and item 5 was rated as 1 (very much satisfied), 2 (much satisfied), 3 (minimally satisfied), 4 (neither satisfied nor dissatisfied), 5 (minimally dissatisfied), 6 (much dissatisfied), 7 (very much dissatisfied). Collapsed ratings: Improved=Very much, much, or minimally improved; Worsened=Very much, much, or minimally worse; No change; Satisfied=Very much, much, or minimally satisfied; Not satisfied=Very much, much, or minimally dissatisfied; No opinion (neither satisfied nor dissatisfied).	Day 21 post injection at week 14
Change in Body Mass Index From Baseline to Week 24 in Part C	Difference in Body Mass Index (BMI) from baseline to week 24 calculated from weight (kg) divided by height squared (m2)	Baseline, Week 24
Change in Weight From Baseline to Week 24 in Part C		Baseline, Week 24
Percentage of Participants With at Least 1 Serum Total Testosterone Concentration >1000, >1100, >1250, and <300 or >1000 ng/dL During the 2nd Injection Interval in Part C2		Days 0, 4, 7, 11, 14, and 70 post injection at week 4
Serum Dihydrotestosterone Concentrations During the 2nd Injection Interval in Part C2		Days 0, 4, 7, 11, 14, and 70 post injection at week 4
Serum Total Testosterone Concentrations in Part C2		Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44
Percentage of Participants With Serum Total Testosterone Concentrations Outside the Normal Range in Part C2	Serum total testosterone concentrations outside the normal range are categorized as <300 ng/dL (below lower limit of normal range) and >1000 ng/dL (above upper limit of normal range)	Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44
Trough Assessments of Serum Total Testosterone Concentrations in Part C2		Screening; day 0; and weeks 4, 14, 24, 34, and 44
Serum Total Testosterone Maximum Concentration in Part C2		Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; and weeks 14, 24, 34, and 44

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Indevus Pharmaceuticals, Inc., Sponsor GmbH

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 27, 2007
• First Submitted That Met QC Criteria: April 27, 2007
• First Posted (Estimate): May 1, 2007

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Hypogonadism; testosterone; investigational; testosterone undecanoate; TU; primary hypogonadism; secondary hypogonadism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: IP157-001