Study to Compare DITEST to Testosterone Undecanoate in Adult Men With Hypogonadism

NCT02966652 | Completed Phase 1 DMC

• 1 other identifier: DITEST-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

DITEST is an oral formulation of native testosterone for the treatment of androgen deficiency in men. The study was a Phase 1 clinical study in hypogonadal men, defined according to FDA and Endocrine Society Guidelines, designed to evaluate the pharmacokinetic (PK) characteristics of DITEST, and to assess the safety and tolerability of DITEST in the target population.

Conditions

Male Hypogonadism

Keywords

Male; Hypogonadism; Primary; Secondary; Androgen deficiency

Outcome Measures

Primary Outcomes (2)

• Testosterone serum concentrations - Peak Plasma Concentration (Cmax)

  Testosterone serum concentrations after administration of a single dose of 120mg or 200mg DITEST and 80mg testosterone undecanoate in the fed state, as measured by the primary PK parameter of Cmax.

  Study day 0 to Study Day >7 (sampling time points at -0.5, 0.25 [120mg and TU arms only], 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8 and 10 hours post-Investigational Medicinal Product (IMP) administration, on each visit date)

• Testosterone serum concentrations - Area under the serum testosterone concentration-time curve from time 0-10 (AUC(0-10))

  Testosterone serum concentrations after administration of a single dose of 120mg or 200mg DITEST and 80mg testosterone undecanoate in the fed state, as measured by the primary PK parameter of AUC.

  Study day 0 to Study Day >7 (sampling time points at -0.5, 0.25 [120mg and TU arms only], 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8 and 10 hours post-IMP administration, on each visit date)

Secondary Outcomes (6)

• Testosterone serum concentrations - Peak serum testosterone Concentration (Cmax)

  Study day 0 to Study Day >7 (sampling time points at -0.5, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8 and 10 hours post-IMP administration, on each visit date)

• Testosterone serum concentrations after 200mg dose - Area under the serum testosterone concentration-time curve (AUC 0-10)

  Study day 0 to Study Day >7 (sampling time points at -0.5, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8 and 10 hours post-IMP administration, on each visit date)

• Adverse events

  Through study completion - a maximum of 84 days.

• Vital signs

  Through study completion - a maximum of 84 days.

• Electrocardiogram (ECG)

  Through study completion - a maximum of 84 days.

Study Arms (2)

Testosterone undecanoate

ACTIVE COMPARATOR

Cohort 1: single dose of 120 mg (3 x 40 mg) DITEST followed by a single dose of 80 mg (2 x 40 mg) testosterone undecanoate or a single dose of 80 mg (2 x 40 mg) testosterone undecanoate followed by single dose of 120 mg (3 x 40 mg) DITEST. The two treatments are separated by a minimum of a 7-day washout period, with both treatments given in the fed state.

Drug: DITEST; Drug: Testosterone undecanoate

DITEST

EXPERIMENTAL

Cohort 2: single dose of 200 mg (5 x 40 mg) DITEST (fed) followed by a single dose of 200 mg DITEST (fasted) or a single dose of 200 mg DITEST (fasted) followed by single dose of 200 mg (5 x 40 mg) DITEST (fed). The two treatments are separated by a minimum of a 7-day washout period.

Drug: DITEST

Interventions

DITEST DRUG

Lipid formulation of native oral testosterone.

DITEST; Testosterone undecanoate

Testosterone undecanoate DRUG

Generic treatment for patients with primary or secondary male hypogonadism

Testosterone undecanoate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects aged 18 to 80 years.
• Diagnosis of primary testicular failure or secondary hypogonadism due to known pituitary disease or congenital deficit.
• Body mass index (BMI) \>18kg/m2 and \<35kg/m2
• Testosterone level \<8nmol/L after washout of current testosterone treatment, if applicable.
• Normal prostate specific antigen (PSA) levels based on the age of the subject.
• Provision of written informed consent and able to participate in the study and abide by the study restrictions.

You may not qualify if:

• Subjects with a past history of, or current prostate cancer, male breast cancer or hepatic neoplasm.
• Subjects with a history of or current myocardial infarction (MI), unstable cardiovascular disease, or clinically relevant findings on the screening electrocardiogram (ECG) (as determined by the investigator)
• Subjects with a history of or current alcohol abuse (consumption of more than 28 units per weekweek: 1 unit equals 25mL single measure of whisky (ABV 40%), a third of a pint of beer (ABV 5-6%) or half a standard (175 mL) glass of red wine (ABV 12%).
• Subjects with other unstable or inadequately treated endocrine conditions.
• Haematocrit levels \>0.5 at baseline
• Subjects with poor dental hygiene that would interfere with the collection of saliva samples or contaminate them with blood.
• Subjects with any severe co-morbidity or with any significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial.
• Allergic to any of the ingredients in the DITEST capsule, particularly sesame oil, or to any components of testosterone undecanoate capsules, particularly castor oil.
• Subjects with a known intolerance to alcohol (e.g. flushing) or ethnic populations at high risk of alcohol dehydrogenase (ADH) enzyme polymorphism with potential to impair metabolism of benzyl alcohol and ethanol, both of which are contained in the DITEST formulation.
• Meeting any of the contraindications for testosterone undecanoate, as detailed in the Summary of Product Characteristics (SmPC) of the comparator product.
• Subjects who are unable to consume the standard high-fat breakfast.
• Subjects who have donated blood or plasma in the previous 3 months prior to screening.
• Any subjects taking a concomitant medication known to enhance or inhibit the action of p450 CYP3A4 (rifampicin, barbiturates, carbamazepine, dichloralphenazone, phenylbutazone, phenytoin or primidone).

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• Sheffield Teaching Hospitals NHS Foundation Trust: collaborator
• Simbec Research: collaborator
• Voet Consulting: collaborator
• EMAS Pharma: collaborator
• Medical Matters International Ltd: collaborator
• Brush Clinical Research Ltd.: collaborator
• Manchester University NHS Foundation Trust: collaborator
• Covance: collaborator

Study Sites (1)

Sheffield Teaching Hospital - Royal Hallamshire Hospital

Sheffield, England, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Eunuchism; Hypogonadism; Neoplasm Metastasis

Interventions

testosterone undecanoate

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• J Newell-Price, MA, PhD

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: November 17, 2016
• Study Start: November 3, 2016
• Primary Completion: October 4, 2018
• Study Completion: October 4, 2018
• Last Updated: November 26, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)