Pilot Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

• Sponsor: Clarus Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02697188
• Collaborator: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
• Enrollment: 12
• Locations: 2
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 6
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Determine the serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU) administered once -(QD) and twice-daily (BID) to hypogonadal men.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism	Drug: Testosterone undecanoate; Drug: Testosterone enanthate	Phase 2

Detailed Description

Five period cross-over study in which subjects received a single day of dosing in each period. Dosing was either QD or BID with one of two T esters (T-enanthate (TE) or T-undecanoate (TU)). Dosing was within 5 minutes of meals (breakfast and for BID dosing dinner). There was a minimum of a 5-day washout between periods. Subjects were hypogonadal men.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIa, Pilot, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Testosterone undecanoate Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose)	Drug: Testosterone undecanoate; Single-day dose as QD or BID for 3 of 5 crossover periods; Other Names: TU
Active Comparator: Testosterone enanthate Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose)	Drug: Testosterone enanthate; Single-day dose for 2 of 5 crossover periods; Other Names: TE

Outcome Measures

Primary Outcome Measures

1. Mean Serum Testosterone Cavg [Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose]

   The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.

Secondary Outcome Measures

1. Mean Serum Dihydrotestosterone Cmax [24 hours post-dose in each period]

   The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Male, ages 18 to 65 Serum total testosterone less than or equal to 250 ng/dL Naive to androgen replacement therapy Subject must be on stable doses of thyroid or adrenal replacement hormones for at least 14 days prior to enrollment

Exclusion Criteria:

Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. Patients with treated hyperlipidemia will not be excluded provided they have been stable on their lipid-lowering mediation for at least three months. For non-insulin dependent diabetic subjects, HbA1c>9%.

Abnormal prostate digital rectal examination, elevated PSA (serum PSA >4ng/mL), AUA Sympton Score greater than or equal to 15 points, and a history or prostate cancer.

Serum transaminases >2X upper limit of normal (ULN) or serum bilirubin >2.0 mg/dL.

History of severe or multiple allergies, severe adverse drug reaction or leucopenia. Known hypersensitivity to lidocaine or all surgical dressings.

History of abnormal bleeding tendencies. Oral, topical, or buccal T therapy within the previous week, or intramuscular T injection within the previous 4 week.

Use of dietary supplements that may increase serum T, such as androstenedione or DHEA, within the previous 4 weeks.

Know malabsorption syndrome and/or current treatment with oral lipase inhibitors, bile acid-binding resins, colestipol, fibric acid derivatives, gemfibrozil, and probucol.

Smokers who are unable to refrain from smoking during confinement periods. History of, or current evidence of, abuse of alcohol or any drug substance. Poor compliers or those unlikely to attend. Receipt of any drug as part of a research study within 30 days of inital dose administration in this study.

Blood donation (usually 550 mL) within the 12-week period before the initial study dose.

Hematocrit less than 35%. Known clinical polycythemia or hematocrit greater than 50%. Current use of paroxetine and clomipramine, antiandrogens, estrogens, p450 enzyme inducers, or barbiturates.

History of sleep apnea.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Los Angeles	California	United States	90502
2	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, MD, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Principal Investigator: Sherwyn Schwartz, MD, dgd Research, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clarus Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02697188
• Other Study ID Numbers: CLAR-07004
• First Posted: Mar 3, 2016
• Last Update Posted: Nov 1, 2018
• Last Verified: Oct 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: 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	Cross over study with 5 periods. Twelve subjects enrolled and completed 5 crossover periods each.

Arm/Group Title	Testosterone Enanthate and Testosterone Undecanoate
Arm/Group Description	Testosterone Enanthate Periods 1 and 5 Single-day dose as QD Period 1 and BID Period 5 Testosterone Undecanoate: Single-day dose as QD Period 2 and BID Periods 3 and 4
Period Title: TE Period 1 - 400 mg QD
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: TE Period 1 - 400 mg QD
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: TE Period 1 - 400 mg QD
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: TE Period 1 - 400 mg QD
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: TE Period 1 - 400 mg QD
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Testosterone Enanthate and Testosterone Undecanoate
Arm/Group Description	Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose) Testosterone enanthate: Single-day dose for 2 of 5 crossover periods Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose) Testosterone undecanoate: Single-day dose as QD or BID for 3 of 5 crossover periods
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 91.7%
>=65 years	1 8.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Mean Serum Testosterone Cavg
Description	The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.
Time Frame	Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Enanthate and Testosterone Undecanoate
Arm/Group Description	Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose) Testosterone enanthate: Single-day dose for 2 of 5 crossover periods Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose) Testosterone undecanoate: Single-day dose as QD or BID for 3 of 5 crossover periods
Measure Participants	12
TE Period 1 400 mg QD	293 (148)
TU Period 2 200 mg QD	246 (77)
TU Period 3 100 mg BID	281 (89)
TU Period 4 200 mg BID	385 (132)
TE Period 5 400 mg BID	316 (167)

2. Secondary Outcome

Title	Mean Serum Dihydrotestosterone Cmax
Description	The objective of the study was to determine the single day serum pharmacokinetic profile for two oral formulations of T-esters (one TE and one TU formulation) administered once- and twice-daily to hypogonadal men.
Time Frame	24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Enanthate and Testosterone Undecanoate
Arm/Group Description	Period 1 - 400 mg T (as TE) QD Period 5 - 800 mg T (as TE) BID (400 mg/dose) Testosterone enanthate: Single-day dose for 2 of 5 crossover periods Period 2 - 200 mg T (as TU) QD Period 3 - 200 mg T (as TU) BID (100 mg/dose) Period 4 - 400 mg T (as TU) BID (200 mg/dose) Testosterone undecanoate: Single-day dose as QD or BID for 3 of 5 crossover periods
Measure Participants	12
TE Period 1 400 mg QD	140 (96)
TU Period 2 200 mg QD	122 (66)
TU Period 3 100 mg BID	97.9 (51.2)
TU Period 4 200 mg BID	114 (58)
TE Period 5 400 mg BID	127 (81)

Adverse Events

Time Frame	Subjects received doses on 5 dosing days spanning approximately 4 weeks.
Arm/Group Title	Testosterone Enanthate 400 mg QD		Testosterone Undecanoate 200 mg QD		Testosterone Undecanoate 100 mg BID		Testosterone Undecanoate 200 mg BID		Testosterone Enanthate 400 mg BID
Arm/Group Description	Period 1: Testosterone Enanthate 400 mg QD		Period 2: Testosterone Undecanoate 200 mg QD		Period 3: Testosterone Undecanoate 100 mg BID		Period 4: Testosterone Undecanoate 200 mg BID		Period 5: Testosterone Enanthate 400 mg BID
All Cause Mortality
	Testosterone Enanthate 400 mg QD		Testosterone Undecanoate 200 mg QD		Testosterone Undecanoate 100 mg BID		Testosterone Undecanoate 200 mg BID		Testosterone Enanthate 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Testosterone Enanthate 400 mg QD		Testosterone Undecanoate 200 mg QD		Testosterone Undecanoate 100 mg BID		Testosterone Undecanoate 200 mg BID		Testosterone Enanthate 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone Enanthate 400 mg QD		Testosterone Undecanoate 200 mg QD		Testosterone Undecanoate 100 mg BID		Testosterone Undecanoate 200 mg BID		Testosterone Enanthate 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		3/12 (25%)		3/12 (25%)		4/12 (33.3%)		2/12 (16.7%)
Blood and lymphatic system disorders
Anemia	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	2
Gastrointestinal disorders
indigestion	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
General disorders
headache	1/12 (8.3%)	1	0/12 (0%)	0	2/12 (16.7%)	2	1/12 (8.3%)	1	0/12 (0%)	0
lethargic	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
night sweats	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Infections and infestations
upper respiratory tract infection	1/12 (8.3%)	1	2/12 (16.7%)	2	3/12 (25%)	3	4/12 (33.3%)	4	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Gout	1/12 (8.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.