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

Phase II, Repeat Dose, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

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.

Study Overview

• Status: Completed
• Conditions: Hypogonadism
• Intervention / Treatment: 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)

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics
    • Birmingham, Alabama, United States, 35235
      • Alabama Internal Medicine
  • California
    • Los Angeles, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Dgd Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Testosterone Average Concentration (Cavg) (ng/dL)	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.	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
Serum Testosterone Area Under Curve (AUC) (0-24) (ng•hr/dL)	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.	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

Collaborators and Investigators

• Sponsor: Clarus Therapeutics, Inc.
• Collaborators: 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.

Publications and helpful links

General Publications

• Yin AY, Htun M, Swerdloff RS, Diaz-Arjonilla M, Dudley RE, Faulkner S, Bross R, Leung A, Baravarian S, Hull L, Longstreth JA, Kulback S, Flippo G, Wang C. Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation. J Androl. 2012 Mar-Apr;33(2):190-201. doi: 10.2164/jandrol.111.013169. Epub 2011 Apr 7.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): August 1, 2009

Study Registration Dates

• First Submitted: June 9, 2008
• First Submitted That Met QC Criteria: June 10, 2008
• First Posted (ESTIMATE): June 11, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: testosterone; male hypogonadism; low testosterone
• 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: CLAR-08005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO