The Effect of Various Amounts of Fat on PK of Oral Testosterone Undecanoate

NCT02921386 | Completed Phase 2 Results

• 1 other identifier: CLAR-16015
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 2, open-label, randomized, cross-over, pharmacokinetic study designed to determine the effect of meals of various amounts of fat given immediately prior to dosing on the pharmacokinetics of oral testosterone undecanoate. Approximately 20 hypogonadal subjects will be dosed for a 14 day run-in period. This will be followed by a randomized sequence of five periods over a 6 day confinement period. Subjects will receive a randomly ordered sequence of breakfast meals containing various amounts of fat, fasting, 15 g, 30 g, 45 g and a high fat breakfast consistent Guidance for Industry on Food-Effect Bioavailability and Fed Bioequivalence Studies.

Conditions

Hypogonadism

Outcome Measures

Primary Outcomes (4)

• Cmax-am for Oral TU Across Breakfast With Varying Fat Content

  Peak Concentration after morning dose (Cmax) for oral testosterone undecanoate taken after a fasting breakfast of varying fat content.

  0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

• Time of Peak Concentration (Tmax-am)

  The time of peak concentration (Tmax-am) will be assessed within each relevant dosing interval.

  12 hours

• Area Under the Curve (AUC-am)

  The 12 hours following morning dose area under the curve (AUC) will assessed for each sequence of breakfasts with varying fat content.

  0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

• Time Weighted Average Total Testosterone Concentration (Cavg-am)

  The time weighted average of total testosterone concentration will be assessed for each dosing interval.

  12 hours

Study Arms (5)

Breakfast A - Fasting

OTHER

Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to Fasting at breakfast and immediately prior to dinner.

Drug: Oral Testosterone Undecanoate

Breakfast B - 15 g fat

OTHER

Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 15 g fat breakfast and immediately prior to dinner.

Drug: Oral Testosterone Undecanoate

Breakfast C - 30 g fat

OTHER

Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 30 g fat breakfast and immediately prior to dinner.

Drug: Oral Testosterone Undecanoate

Breakfast D - 45 g fat

OTHER

Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 45 g fat breakfast and immediately prior to dinner.

Drug: Oral Testosterone Undecanoate

Breakfast E - High Fat

OTHER

Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to high fat breakfast and immediately prior to dinner.

Drug: Oral Testosterone Undecanoate

Interventions

Oral Testosterone Undecanoate DRUG

All study participants received Oral TU dose of 237 mg TU twice daily before breakfast and dinner for 14 days and throughout 5 crossover periods

Breakfast A - Fasting; Breakfast B - 15 g fat; Breakfast C - 30 g fat; Breakfast D - 45 g fat; Breakfast E - High Fat

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man 18 to 65 years of age, inclusive, with a clinical diagnosis of hypogonadism (signs/symptoms consistent with hypogonadism for testosterone naïve subjects and history of signs/symptoms for subjects who have received prior treatment) as well as testosterone levels consistent with hypogonadism as defined by 2 morning total T values of \<300 ng/dL (between 6:00 and 10:00 AM drawn on 2 separate days \[approximately 7 (±2) days apart\].
• Adequate venous access in the left or right arm to allow collection of a number of blood samples via a venous cannula.
• 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.
• Has voluntarily given written informed consent to participate in this study.

You may not qualify if:

• Received oral topical (eg, gel or patch), intranasal, or buccal T therapy within the previous 2 weeks, intramuscular T injection of short-acting duration (eg, T enanthate, T cypionate) within the previous 4 weeks, intramuscular T injection of long-acting duration (eg, AVEED) within the previous 20 weeks, or T implantable pellets (Testopel®) within the previous 6 months.
• Has an intercurrent disease deemed clinically significant in the opinion of the investigator 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.
• Has had a recent (within 2 years) history of stroke, transient ischemic attack, or acute coronary event.
• Has a mean of the triplicate assessment of sBP \> 150 mm Hg and/or dBP \> 90 mm Hg at screening (if prescribed antihypertensives, subject should be taking medications on the day of the screening visit with a sip of water). Subjects \< 60 years of age and prescribed antihypertensives will be excluded if the mean of the triplicate assessment of sBP \> 140 mm Hg and/or dBP \> 90 mm Hg at screening.
• Has had recent (within 2 years) history of angina or stent (coronary or carotid) placement.
• Has untreated, severe obstructive sleep apnea.
• Has clinically significant abnormal laboratory values, including serum transaminases \> 2 × upper limits of normal (ULN), serum bilirubin \> 1.5 × ULN and serum creatinine \> 1.5 × ULN.
• Has a hematocrit (HCT) value of \< 35% or \> 48%.
• Has a history of polycythemia, either idiopathic or associated with TRT treatment.
• Is a diabetic subject with a glycosylated hemoglobin \> 8.5%.
• Has a body mass index (BMI) ≥ 38 kg/m2.
• Has been on stable doses of antihypertensive medication for \< 3 months.
• Has an abnormal prostate digital rectal examination \[(DRE); palpable nodules\], elevated PSA (serum PSA \> 4.0 ng/mL), I-PSS \> 19 points at screening, and/or history of, or current or suspected, prostate cancer.
• Has a history of, or current or suspected, breast cancer.
• Has a history of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation within the previous 2 years.

Sponsors & Collaborators

• Clarus Therapeutics, Inc.: lead
• Celerion: collaborator

Study Sites (2)

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809-3017, United States

Location

MeSH Terms

Conditions

Hypogonadism

Interventions

testosterone undecanoate

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Theodore Danoff, MD, PhD
• Organization: Clarus Therapeutics Inc.

tdanoff@clarustherapeutics.com

847-562-4300

Study Officials

• Ronald Swerdloff

  Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, randomized, 5-period crossover food effect study

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: October 3, 2016
• Study Start: October 1, 2016
• Primary Completion: January 21, 2017
• Study Completion: January 21, 2017
• Last Updated: May 17, 2018
• Results First Posted: April 12, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)