Open-label, Follow-up Study of Oral Testosterone Undecanoate in Hypogonadal Men

Open-Label Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01699178

Enrollment

182

Registered

2012-10-03

Start date

2012-08-31

Completion date

2014-04-30

Last updated

2021-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Male Hypogonadism

Brief summary

The purpose of this one year extension (follow-up) study is to gather additional safety data in hypogonadal men treated with oral TU or AndroGel who have completed the 12-month Phase III study CLAR-09007.

Detailed description

This is the long-term extension of Study CLAR-09007, which like Study CLAR-09007, is an open-label study. This study contained an arm to evaluate the oral TU formulation as well as a comparator arm of the market-leading transdermal T-gel formulation. The comparator arm was included in the Phase III study and in this extension study to allow a general evaluation of comparative safety. Subjects randomized to oral TU in the Phase III study were continued on oral TU in the extension, and those who completed this 12-month Phase IV study have been followed for a total of 2 years of oral TU therapy. Likewise, subjects randomized to transdermal T-gel in the Phase III study were continued on T-gel in the extension, and those who completed this 12-month Phase IV study have been followed for a total of 2 years of T gel therapy. This 2-year period of therapy and assessments was to provide a long-term view of the safety of oral TU and the stability of the T replacement.

Interventions

DRUGOral testosterone undecanoate

Total daily dose of T = 200 mg T (as 316 mg TU) to 600 mg T (as 948 mg TU), taken as 100 mg to 300 mg T BID

DRUGTransdermal testosterone gel (AndroGel)

Total daily dose of T = 2.5 to 10 g of gel (25 mg to 100 mg T) QD

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Subjects were to have completed Study CLAR-09007. 2. Subjects were to have adequate venous access in the left or right arm to allow collection of a number of blood samples via a venous cannula. 3. Subjects were required to remain off all forms of T except for study medication throughout the entire study. 4. Subjects voluntarily gave written informed consent to participate in this study. Subjects meeting any of the following criteria were not eligible for participation in this study: 1. Significant intercurrent disease of any type, in particular liver, kidney, uncontrolled or poorly controlled heart disease, or psychiatric illness developed during the Phase III study that would, in the opinion of the Investigator, require exclusion from this study. 2. Untreated, severe obstructive sleep apnea (diagnosed during previous Phase III study). 3. Serum transaminases \>2 times upper limit of normal (ULN), serum bilirubin \>2.0 mg/dL and serum creatinine \>2.0 mg/dL at the final visit for Study CLAR 09007. 4. Abnormal prostate digital rectal examination (palpable nodule\[s\]) or elevated PSA (serum PSA \>4 ng/mL) at the final visit for Study CLAR-09007. 5. Use of dietary supplement saw palmetto or phytoestrogens and use of any dietary supplements that may increase serum T, such as androstenedione or dehydroepiandrosterone (DHEA). 6. Known malabsorption syndrome and/or current treatment with oral lipase inhibitors (e.g., orlistat \[Xenical\]) and bile acid-binding resins (e.g., cholestyramine \[Questran\], colestipol \[Colestid\]). 7. Poor compliers with study medication, study procedures, or study visits in Study CLAR 09007. 8. Concomitant use of antiandrogens, estrogens, potent oral CYP3A4 inducers (e.g., barbiturates, glucocorticoids \[pharmacologic doses of glucocorticoids for replacement therapy were not exclusionary\]) and potent CYP3A4 inhibitors (e.g., human immunodeficiency virus \[HIV\] antivirals \[indinavir, nelfinavir, ritonavir, saquinavir, delaviridine\], amiodarone, azithromycin, ciprofloxacin, ketoconazole). (Note: Short-term ciprofloxacin administration completed more than 7 days prior to study visits was not exclusionary during the study.)

Design outcomes

Primary

Measure	Time frame	Description
Absolute Change From Baseline in T Cholesterol	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.
Absolute Change From Baseline in HDL	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.
Absolute Change From Baseline in LDL	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.
Absolute Change From Baseline in Hgb	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.
Absolute Change From Baseline in Hct	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.
Absolute Change From Baseline in Prostate Volume	Approximately 365 days	Long-term safety profile of oral TU product compared with AndroGel based on absolute change from primary baseline based on Total Cholesterol, HDL, LDL, hemoglobin, hematocrit and prostate volume.

Countries

Germany, United States

Participant flow

Participants by arm

Arm	Count
Oral Testosterone Undecanoate Oral testosterone undecanoate; continue dose from previous Phase III trial; 100-300 mg T (as TU), BID, for 12 months. Oral testosterone undecanoate: Total daily dose of T = 200 mg T (as 316 mg TU) to 600 mg T (as 948 mg TU), taken as 100 mg to 300 mg T BID	88
Transdermal Testosterone Gel (AndroGel) Transdermal testosterone gel; continue dose from previous Phase III trial, 2.5-10 g/applied once daily for 12 months Transdermal testosterone gel (AndroGel): Total daily dose of T = 2.5 to 10 g of gel (25 mg to 100 mg T) QD	94
Total	182

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	5
Overall Study	Hematocrit >54%	1	1
Overall Study	ineligible/noncompliant/ subject reason	4	4
Overall Study	Lost to Follow-up	1	6
Overall Study	Non-compliance with Study Drug	3	1
Overall Study	Physician Decision	1	0
Overall Study	PSA increase of >1.4 ng/mL	4	3
Overall Study	Withdrawal by Subject	4	12

Baseline characteristics

Characteristic	Transdermal Testosterone Gel (AndroGel)	Oral Testosterone Undecanoate	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	94 Participants	88 Participants	182 Participants
Age, Continuous	56.8 years STANDARD_DEVIATION 11.23	56.2 years STANDARD_DEVIATION 10.04	56.5 years STANDARD_DEVIATION 10.64
Region of Enrollment United States	94 participants	88 participants	182 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	94 Participants	88 Participants	182 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 88	0 / 94
other Total, other adverse events	32 / 88	33 / 94
serious Total, serious adverse events	6 / 88	6 / 94