Pharmacokinetic Study of Oral Testosterone (T) Ester Formulations in Hypogonadal Men

• Sponsor: Clarus Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00695110
• Collaborator: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
• Enrollment: 29
• Locations: 4
• Arm: 1
• Duration (Months): 14
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this pharmacokinetic study is to determine whether oral testosterone (T) ester formulations can be used effectively to treat men with low testosterone.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism	Drug: Oral testosterone undecanoate (TU) (300 mg T equivalents/dose); Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose); Drug: Oral testosterone undecanoate (TU) (200 mg T equivalents/dose with and without food); Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose)	Phase 2

Detailed Description

Determination of the steady-state serum T pharmacokinetic profiles for two oral formulations of T-esters [testosterone undecanoate (TU) and TU combined with testosterone enanthate (TE)] administered bis in die (BID) to 29 hypogonadal adult male subjects. TU was evaluated in total daily doses of 400 and 600 mg equivalents of T given twice daily for 7 or 8 days; TU + TE was evaluated in total daily doses of 600 and 800 mg equivalents of T given twice daily for 7 days. All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner. In Treatment Period 3 the effect of food on the study-state pharmacokinetics profile of the TU formulation was evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner.All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Repeat Dose, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: All study participants Treatment Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), twice daily (BID) for 7 days. Treatment Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID for 7 days. Treatment Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days. Treatment Period 4: Two capsules each containing 150 mg T as TU and TE, BID for 7 days.

Drug: Oral testosterone undecanoate (TU) (300 mg T equivalents/dose); Three capsules each containing 100 mg testosterone (T) as TU, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.; Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose); Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.; Drug: Oral testosterone undecanoate (TU) (200 mg T equivalents/dose with and without food); Two capsules each containing 100 mg T as TU, BID for 8 days. 200 mg T equivalents BID 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.; Drug: Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose); Two capsules each containing 150 mg T as TU and 150 mg T as TE, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days.

Outcome Measures

Primary Outcome Measures

1. Serum Testosterone Average Concentration (Cavg) (ng/dL) [30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses]

   Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3.

2. Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL) [30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses]

   Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 68 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male, ages 18-68

• Serum total T less than or equal to 275 ng/dL

Exclusion Criteria:

• Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness.

• Abnormal prostate digital rectal examination, elevated prostate-specific antigen (PSA), American Urological Association (AUA) symptom score of >15, and/or history of prostate cancer.

• Hematocrit of <35 or >50%

• Body mass index (BMI) >36

• Serum transaminases > 2 times upper limit of normal or serum bilirubin > 2.0 mg/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35235
2	Alabama Internal Medicine	Birmingham	Alabama	United States	35235
3	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Los Angeles	California	United States	90502
4	dgd Research, Inc.	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Clarus Therapeutics, Inc.
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

• Principal Investigator: Ronald S Swerdloff, M.D., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Principal Investigator: Gregory Flippo, M.D., Alabama Clinical Therapeutics, Inc.
• Principal Investigator: Steven J. Kulback, M.D., Alabama Internal Medicine
• Principal Investigator: Sherwyn Schwartz, M.D., dgd Research, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clarus Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT00695110
• Other Study ID Numbers: CLAR-08005
• First Posted: Jun 11, 2008
• Last Update Posted: Jun 25, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Clarus Therapeutics, Inc.: testosterone; male hypogonadism; low testosterone
• Additional relevant MeSH terms: Hypogonadism; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Recruitment Details

A total of 45 subjects were screened at 4 study sites (1 university medical center and 3 clinical sites). 29 hypogonadal males met all eligibility requirements and were enrolled with first study drug administration on June 13, 2008.

Pre-assignment Detail

After signing an informed consent form, subjects underwent a screening evaluation up to 28 days prior to the first dose of study drug. 29 subjects meeting the admission criteria, began Treatment Period 1 intervention (7 days) followed by a 7-14 day washout period and then proceeded to Treatment Periods 2-4. A 7-14 day washout period occurred between successive Treatment Periods. Treatment Periods 1, 2, and 4 had intervention for 7 days and Treatment Period 3 had intervention for 8 days.

Arm/Group Title	All Study Participants
Arm/Group Description	Repeat dose, single-group study including 4 treatment periods with a 7-14 day washout between successive periods: Treatment Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Treatment Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Treatment Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days except for Day 8 when the morning dose was administered fasting. Treatment Period 4: Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Period Title: Treatment Period 1
STARTED	29
COMPLETED	26
NOT COMPLETED	3
Period Title: Treatment Period 1
STARTED	26
COMPLETED	26
NOT COMPLETED	0
Period Title: Treatment Period 1
STARTED	26
COMPLETED	25
NOT COMPLETED	1
Period Title: Treatment Period 1
STARTED	25
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Repeat dose, sequential cross-over study including 4 treatment periods with a 7-14 day washout between successive periods: Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days except for Day 8 when the morning dose was administered fasting. Period 4: Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.6 (10.23)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	29 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 20.7%
Not Hispanic or Latino	23 79.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 6.9%
White	27 93.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Total Testosterone (ng/dL) (ng/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/dL]	169.0 (82.80)
Body Mass Index (BMI) (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.4 (3.43)
Height (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	69.9 (4.0)
Weight (pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pounds]	212.2 (38.68)

Outcome Measures

1. Primary Outcome

Title	Serum Testosterone Average Concentration (Cavg) (ng/dL)
Description	Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3.
Time Frame	30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses

Outcome Measure Data

Analysis Population Description

All available individual serum concentrations and pharmacokinetic parameter estimates were reported; missing data were not imputed. For 1 subject in Treatment Period 1 and 1 subject in Treatment Period 4 there were insufficient data to calculate all pharmacokinetic parameters.

Arm/Group Title	Treatment Period 1	Treatment Period 2	Treatment Period 3	Treatment Period 4
Arm/Group Description	Oral testosterone undecanoate (TU) (300 mg T equivalents/dose): Three capsules each containing 100 mg testosterone (T) as TU, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose): Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) (200 mg T equivalents/dose) with and without food): Two capsules each containing 100 mg T as TU, BID for 8 days 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose): Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Measure Participants	28	26	26	24
Cavg (0-24)	792 (254)	654 (230)	541 (289)
Cavg (AM dose) with food	765 (333)	657 (294)	518 (233)	533 (385)
Cavg (PM dose) with food	819 (291)	651 (236)	548 (250)
Cavg (AM dose) fasting	241 (106)

2. Primary Outcome

Title	Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL)
Description	Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3.
Time Frame	30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses

Outcome Measure Data

Analysis Population Description

All available individual serum concentrations and pharmacokinetic parameter estimates were reported; missing data were not imputed. For 1 subject in Treatment Period 1 and 1 subject in Treatment Period 4 there were insufficient data to calculate all pharmacokinetic parameters.

Arm/Group Title	Treatment Period 1	Treatment Period 2	Treatment Period 3	Treatment Period 4
Arm/Group Description	Oral testosterone undecanoate (TU) (300 mg T equivalents/dose): Three capsules each containing 100 mg testosterone (T) as TU, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose): Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) (200 mg T equivalents/dose) with and without food): Two capsules each containing 100 mg T as TU, BID for 8 days 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.	Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose): Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days.
Measure Participants	28	26	26	24
AUC (0-24)	19009 (6102)	15693 (5527)	12980 (6926)
AUC (0-12) (AM dose) with food	9179 (3990)	7881 (3524)	6217 (2792)	6601 (4614)
AUC (12-24) (PM dose) with food	9830 (3489)	7812 (2837)	2894 (1267)
AUC (0-12) (AM dose) fasting	2894 (1267)

Adverse Events

Time Frame	Adverse Events, whether observed by the investigator, elicited during telephone contacts and/or study visits, reported in response to a query, or reported spontaneously by the subject were recorded from time of informed consent throughout Treatment Periods 1-4 (7-8 days/period) and all 7-14 day washout periods between treatment periods totaling approximately 100 days.
Arm/Group Title	All Study Participants
Arm/Group Description	Single group, repeat dose study including 4 treatment periods (7-8 days) and a 7-14 day washout between successive periods: Treatment Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Treatment Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. Treatment Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days except for Day 8 when the morning dose was administered fasting. Treatment Period 4: Two capsules each containing 150 mg T as TU and TE, BID, 30 minutes after initiation of breakfast and dinner meals for 7 days. The primary purpose of the study was to evaluate the pharmacokinetics of T following short-term, repeat-dose administration of various T doses in the form of TU or as a combination of TU + TE (7-8 days). Consequently, the AEs represent the integrated sum over all of the treatment groups in what was short-term T exposure compared to long-term efficacy and safety evaluations. Due to the short-term exposure to each intervention, changes in laboratory parameters were assessed at the end of the overall study and not the end of each treatment intervention.
All Cause Mortality
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/29 (0%)
Serious Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)
Infections and infestations
Osteomyelitis	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	19/29 (65.5%)
Blood and lymphatic system disorders
Anemia	1/29 (3.4%)	1
Gastrointestinal disorders
Constipation	2/29 (6.9%)	2
Emesis	1/29 (3.4%)	1
Gastrointestinal reflux	2/29 (6.9%)	3
Nausea	2/29 (6.9%)	2
Nausea and vomiting	1/29 (3.4%)	1
General disorders
Fatigue	2/29 (6.9%)	2
Hunger	1/29 (3.4%)	1
Infections and infestations
Bronchitis	1/29 (3.4%)	1
Sinusitis	1/29 (3.4%)	1
Pharyngitis	2/29 (6.9%)	2
Upper respiratory infection	2/29 (6.9%)	2
Viral herpes simplex	1/29 (3.4%)	1
Investigations
Increased AST and ALT	1/29 (3.4%)	1
Metabolism and nutrition disorders
Diabetes mellitus	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/29 (6.9%)	2
Elbow pain	1/29 (3.4%)	1
Hip pain	1/29 (3.4%)	1
Pain in jaw	1/29 (3.4%)	1
Lower back pain	1/29 (3.4%)	1
Shoulder pain	1/29 (3.4%)	1
Nervous system disorders
Dizziness	1/29 (3.4%)	1
Headache	7/29 (24.1%)	8
Vertigo	1/29 (3.4%)	1
Psychiatric disorders
Insomnia	1/29 (3.4%)	1
Mood altered	1/29 (3.4%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/29 (3.4%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/29 (6.9%)	2
Nasal congestion	3/29 (10.3%)	3
Skin and subcutaneous tissue disorders
Rash	1/29 (3.4%)	1
Vascular disorders
Hypertension	1/29 (3.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 30 days from the time submitted to the sponsor for review. If the communication contains subject matter for which patent protection should be sought, the Sponsor will notify the PI whereupon the PI agrees to grant the Sponsor an additional 60 days to file documents necessary to protect such invention.