Back to resultsA Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men (inTUne)
Primary Purpose
Hypogonadism
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Oral Testosterone Undecanoate
Axiron Testosterone Topical Solution
Sponsored by
About this trial
This is an interventional basic science trial for Hypogonadism
Eligibility Criteria
Inclusion Criteria:
- Man 18 to 65 years of age, inclusive, with hypogonadism as defined by 2 AM total T values of <300 ng/dL drawn on 2 separate days ([approximately 7 days apart]).
- Adequate venous access
- Must be naïve to androgen-replacement therapy or washed out of prior androgen replacement therapies; willing to cease current T treatment or currently not be taking T treatment. Subjects must remain off all forms of T, except for dispensed study drug, throughout the entire study.
- Subjects on replacement therapy for hypopituitarism or multiple endocrine deficiencies must be on stable doses of thyroid hormone and adrenal replacement hormones for at least 14 days before Screen 1.
- Voluntarily given written informed consent to participate in this study.
Exclusion Criteria:
- Received oral topical, intranasal, or buccal T therapy within the previous 2 weeks, intramuscular T injection of short-acting duration within the previous 4 weeks, intramuscular T injection of long-acting duration within the previous 20 weeks, or T implantable pellets within the previous 6 months.
- Received oral TU in a previous Clarus-sponsored investigational study.
- Significant intercurrent disease of any type; in particular, liver, kidney, uncontrolled or poorly controlled heart disease, including hypertension, congestive heart failure or coronary heart disease, or psychiatric-illness, including severe depression.
- Recent (within 2 years) history of stroke, transient ischemic attack, or acute coronary event.
- A mean of the triplicate assessment of systolic blood pressure (sBP) > 150 mm Hg and/or diastolic blood pressure (dBP) > 90 mm Hg at screening.
- Recent (within 2 years) history of angina or stent (coronary or carotid) placement.
- Untreated, severe obstructive sleep apnea.
- Clinically significant abnormal laboratory values (serum transaminases > 2 × ULN, serum bilirubin > 1.5 × ULN and serum creatinine > 1.5 × ULN).
- Hematocrit (HCT) value of < 35% or > 48%.
- Has a history of polycythemia, either idiopathic or associated with testosterone replacement therapy (TRT).
- Glycosylated hemoglobin (A1C) > 8.5%.
- BMI ≥ 38 kg/m2.
If receiving the following medications:
- Has been on stable doses of lipid-lowering medication for < 3 months;
- Has been on stable doses of oral medication for diabetes for < 2 months; or
- Has been on stable doses of antihypertensive medication for < 3 months.
- Abnormal prostate digital rectal examination (palpable nodules), elevated Prostate Specific Antigen (serum PSA > 4.0 ng/mL), International Prostate Symptom Score (I-PSS) > 19 points at screening, and/or history of, or current or suspected, prostate cancer.
- History of, or current or suspected, breast cancer.
- History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation within the previous 2 years.
- Use of dietary supplements such as saw palmetto or phytoestrogens and any dietary supplements that may increase total T, such as androstenedione or dehydroepiandrosterone within the previous 4 weeks.
- Known malabsorption syndrome and/or current treatment with oral lipase inhibitors and bile acid-binding resins.
- Inability to refrain from smoking during the confinement periods as required by the individual study center.
- History of alcohol abuse or any drug substance within the previous 2 years.
- Poor compliance or unlikely to keep clinic appointments.
- Has received any drug as part of another research study within 30 days of initial dose administration in this study.
- Donated blood (≥ 500 mL) within the 12-week period before the initial study dose.
- Currently uses antiandrogens, 5-alpha-reductase inhibitors, estrogens, potent oral CYP3A4 inducers, potent CYP3A4 inhibitors, or long acting opioid analgesics.
- Unwilling or unable to follow the dietary guidelines for this study, related to taking oral TU with meals that contain approximately 20 to 40 g of fat
Sites / Locations
- Multiple Sites in the United States
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Oral Testosterone Undecanoate
Axiron Testosterone Topical Solution
Arm Description
Approximately 135 subjects will receive oral TU treatment during the study for approximately 3.5 months. Subjects randomly assigned to the oral TU treatment group will begin treatment at a dose of 237 mg TU twice daily (BID).
Subjects randomly assigned to the Axiron treatment group will begin treatment at a dose of 60 mg every morning.
Outcomes
Primary Outcome Measures
Number of Oral TU Treated Subjects Who Have a Total T Cavg in the Eugonadal Range of 252 to 907 ng/dL at Visit 7
Secondary Outcome Measures
Full Information
NCT ID
NCT02722278
First Posted
February 15, 2016
Last Updated
January 24, 2018
Sponsor
Clarus Therapeutics, Inc.
Collaborators
Syneos Health
1. Study Identification
Unique Protocol Identification Number
NCT02722278
Brief Title
A Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Acronym
inTUne
Official Title
A Phase 3, Randomized, Active-controlled, Open-label Study of the Safety and Efficacy of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clarus Therapeutics, Inc.
Collaborators
Syneos Health
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A Phase 3, Randomized, Active-controlled, Open-label Study of the Safety and Efficacy of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Detailed Description
This is a multicenter, Phase 3, randomized, open-label, active-comparator group, efficacy (based on Cavg of T), and safety study in adult hypogonadal male subjects. Enrollment is based on criteria designed to select the general population of hypogonadal men. Study drug doses will be titrated using a dose-titration algorithm based on total T Cavg. Subjects may be androgen treatment-naïve or washed out of prior androgen replacement therapies.
Subjects must have 2 total T levels < 300 ng/dL based on 2 blood samples obtained in the morning (AM) on 2 separate days approximately 7 days apart.
Approximately 180 subjects will be randomly assigned to receive open-label treatment in a 3:1 ratio of oral TU to Axiron (ie, approximately 135 subjects will be randomly assigned to oral TU and approximately 45 subjects will be randomly assigned to Axiron topical solution). Subjects who complete the study will receive approximately 105 days of treatment. Dose titrations will be based on the T Cavg from serial PK sampling obtained on day 21 and 56 of treatment. Primary efficacy will be based on percentage of subjects within eugonadal range at Visit 7.
A subset of approximately 30 subjects will participate in a cosyntropin stimulation test on Day 1 (before administration of study drug) and Day 106 after the last 24-hour PK sample has been drawn.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
222 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral Testosterone Undecanoate
Arm Type
Experimental
Arm Description
Approximately 135 subjects will receive oral TU treatment during the study for approximately 3.5 months. Subjects randomly assigned to the oral TU treatment group will begin treatment at a dose of 237 mg TU twice daily (BID).
Arm Title
Axiron Testosterone Topical Solution
Arm Type
Active Comparator
Arm Description
Subjects randomly assigned to the Axiron treatment group will begin treatment at a dose of 60 mg every morning.
Intervention Type
Drug
Intervention Name(s)
Oral Testosterone Undecanoate
Other Intervention Name(s)
Oral TU
Intervention Description
Subjects assigned to oral TU treatment will begin at 237 mg TU twice daily. Serial PK samples over 24 hours will be obtained after 21 days and 56 days of treatment. Dose adjustments may be made on Day 35 and Day 70, based on the T Cavg results obtained at Day 21 and Day 56, respectively. Dose will be increased if Cavg < 350 ng/dL, decreased if > 800 ng/dL and maintained if Cavg = 350 ng/dL to 800 ng/dL.
Intervention Type
Drug
Intervention Name(s)
Axiron Testosterone Topical Solution
Other Intervention Name(s)
Axiron solution
Intervention Description
Subjects assigned to Axiron treatment will begin at 60 mg Axiron every morning. Axiron is applied to the axilla only.
Serial PK samples over 24 hours will be obtained after 21 days and 56 days of treatment. Dose adjustments may be made on Day 35 and Day 70, based on the T Cavg results obtained at Day 21 and Day 56, respectively. Dose will be increased if Cavg < 350 ng/dL, decreased if > 800 ng/dL and maintained if Cavg = 350 ng/dL to 800 ng/dL.
Primary Outcome Measure Information:
Title
Number of Oral TU Treated Subjects Who Have a Total T Cavg in the Eugonadal Range of 252 to 907 ng/dL at Visit 7
Time Frame
Day 105
Other Pre-specified Outcome Measures:
Title
Number of Participants With Post-stimulation Cortisol Level of >18 ug/dL at Visit 8
Description
Compare the Oral TU-treated subjects and the Topical Axiron®-treated subjects with respect to number of subjects in the cosyntropin stimulation test substudy with a normal maximum post-stimulation (cosyntropin stimulation) cortisol level at Visit 8.
Time Frame
Approximately 4.5 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Man 18 to 65 years of age, inclusive, with hypogonadism as defined by 2 AM total T values of <300 ng/dL drawn on 2 separate days ([approximately 7 days apart]).
Adequate venous access
Must be naïve to androgen-replacement therapy or washed out of prior androgen replacement therapies; willing to cease current T treatment or currently not be taking T treatment. Subjects must remain off all forms of T, except for dispensed study drug, throughout the entire study.
Subjects on replacement therapy for hypopituitarism or multiple endocrine deficiencies must be on stable doses of thyroid hormone and adrenal replacement hormones for at least 14 days before Screen 1.
Voluntarily given written informed consent to participate in this study.
Exclusion Criteria:
Received oral topical, intranasal, or buccal T therapy within the previous 2 weeks, intramuscular T injection of short-acting duration within the previous 4 weeks, intramuscular T injection of long-acting duration within the previous 20 weeks, or T implantable pellets within the previous 6 months.
Received oral TU in a previous Clarus-sponsored investigational study.
Significant intercurrent disease of any type; in particular, liver, kidney, uncontrolled or poorly controlled heart disease, including hypertension, congestive heart failure or coronary heart disease, or psychiatric-illness, including severe depression.
Recent (within 2 years) history of stroke, transient ischemic attack, or acute coronary event.
A mean of the triplicate assessment of systolic blood pressure (sBP) > 150 mm Hg and/or diastolic blood pressure (dBP) > 90 mm Hg at screening.
Recent (within 2 years) history of angina or stent (coronary or carotid) placement.
Untreated, severe obstructive sleep apnea.
Clinically significant abnormal laboratory values (serum transaminases > 2 × ULN, serum bilirubin > 1.5 × ULN and serum creatinine > 1.5 × ULN).
Hematocrit (HCT) value of < 35% or > 48%.
Has a history of polycythemia, either idiopathic or associated with testosterone replacement therapy (TRT).
Glycosylated hemoglobin (A1C) > 8.5%.
BMI ≥ 38 kg/m2.
If receiving the following medications:
Has been on stable doses of lipid-lowering medication for < 3 months;
Has been on stable doses of oral medication for diabetes for < 2 months; or
Has been on stable doses of antihypertensive medication for < 3 months.
Abnormal prostate digital rectal examination (palpable nodules), elevated Prostate Specific Antigen (serum PSA > 4.0 ng/mL), International Prostate Symptom Score (I-PSS) > 19 points at screening, and/or history of, or current or suspected, prostate cancer.
History of, or current or suspected, breast cancer.
History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation within the previous 2 years.
Use of dietary supplements such as saw palmetto or phytoestrogens and any dietary supplements that may increase total T, such as androstenedione or dehydroepiandrosterone within the previous 4 weeks.
Known malabsorption syndrome and/or current treatment with oral lipase inhibitors and bile acid-binding resins.
Inability to refrain from smoking during the confinement periods as required by the individual study center.
History of alcohol abuse or any drug substance within the previous 2 years.
Poor compliance or unlikely to keep clinic appointments.
Has received any drug as part of another research study within 30 days of initial dose administration in this study.
Donated blood (≥ 500 mL) within the 12-week period before the initial study dose.
Currently uses antiandrogens, 5-alpha-reductase inhibitors, estrogens, potent oral CYP3A4 inducers, potent CYP3A4 inhibitors, or long acting opioid analgesics.
Unwilling or unable to follow the dietary guidelines for this study, related to taking oral TU with meals that contain approximately 20 to 40 g of fat
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald Swerdloff, MD
Organizational Affiliation
Primary Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Multiple Sites in the United States
City
Northbrook
State/Province
Illinois
ZIP/Postal Code
60062
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Individual patient data will be shared with all principal investigators following the completion of data analyses
Learn more about this trial
A Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
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