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

Primary Purpose

Male Hypogonadism

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

DITEST

Testosterone undecanoate

About this trial

This is an interventional treatment trial for Male Hypogonadism focused on measuring Male, Hypogonadism, Primary, Secondary, Androgen deficiency

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Participation in another clinical trial or an investigation or licensed drug or device within the 3 months prior to inclusion in this study.
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).

Sites / Locations

Sheffield Teaching Hospital - Royal Hallamshire Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Testosterone undecanoate

DITEST

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Testosterone serum concentrations - Peak serum testosterone Concentration (Cmax)

Testosterone serum concentrations after 200mg dose of DITEST in the fed and fasted states, as measured by the primary PK parameter of Cmax.

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

Testosterone serum concentrations after 200mg dose of DITEST in the fed and fasted states, as measured by the primary PK parameter of AUC (0-10)

Adverse events

Adverse events (AEs) observed throughout the study.

Vital signs

Observed changes in vital signs data during the course of the study.

Electrocardiogram (ECG)

Observed changes in ECG data during the course of the study.

Safety Laboratory Data

Observed changes in Safety Laboratory data during the course of the study.

Full Information

NCT ID

NCT02966652

First Posted

September 26, 2016

Last Updated

November 25, 2019

Sponsor

Diurnal Limited

Collaborators

Sheffield Teaching Hospitals NHS Foundation Trust, Simbec Research, Voet Consulting, EMAS Pharma, Medical Matters International Ltd, Brush Clinical Research Ltd., Manchester University NHS Foundation Trust, Covance

1. Study Identification

Unique Protocol Identification Number

NCT02966652

Brief Title

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

Official Title

A Phase 1, Randomised, Open-label, 2-cohort, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Native Oral Testosterone Formulation (DITEST) in the Fed and Fasted State and Compared to Testosterone Undecanoate in Adult Men With Primary or Secondary Hypogonadism

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

November 3, 2016 (Actual)

Primary Completion Date

October 4, 2018 (Actual)

Study Completion Date

October 4, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Diurnal Limited

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

There is an unmet need for a native oral testosterone therapy for men with androgen (testosterone) deficiency. Ideally such a treatment should have reproducible PK, does not need to be taken with fatty meals, can be taken once or twice daily, and provides physiological exposure to testosterone. This Phase 1, randomised, open-label, 2-cohort, cross-over study was therefore designed to evaluate the PK characteristics of DITEST in both the fed and fasted states according to FDA guidelines, and to assess the safety and tolerability of DITEST in the target population. The study was conducted in male subjects from 18 to 80 years of age requiring testosterone replacement therapy for primary or secondary hypogonadism. The study was a randomised, active control, single dose, 2-way cross-over study in 2 cohorts. In each cohort subjects who meet the entry criteria at screening and baseline were randomised to one of 2 sequences: 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 (TU) or a single dose of 80 mg TU followed by single dose of 120 mg DITEST. The two treatments were separated by a minimum of a 7-day washout period, with both treatments given in the fed state. 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 DITEST (fed). The two treatments were separated by a minimum of a 7-day washout period. 13 subjects were recruited into cohort 1 and 12 subjects were recruited into cohort 2, resulting in a total of 25 subjects being administered study medication in this study. Subjects were not recruited into Cohort 2 until the results of subjects treated in Cohort 1 had been evaluated (this review was to determine if the intended dose for Cohort 2 needed to be adjusted). No other testosterone treatments were allowed for the duration of the study (including the washout periods). Each subject was required to attend the study centre for a minimum of either 4 or 5 visits: a screening assessment, an evaluation of baseline testosterone levels after the washout period from the subject's current medication (only for subjects currently on testosterone replacement therapy), both dosing days, and a follow-up visit at the end of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Male Hypogonadism

Keywords

Male, Hypogonadism, Primary, Secondary, Androgen deficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Testosterone undecanoate

Arm Type

Active Comparator

Arm Description

Arm Title

DITEST

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

DITEST

Intervention Description

Lipid formulation of native oral testosterone.

Intervention Type

Drug

Intervention Name(s)

Testosterone undecanoate

Intervention Description

Generic treatment for patients with primary or secondary male hypogonadism

Primary Outcome Measure Information:

Title

Testosterone serum concentrations - Peak Plasma Concentration (Cmax)

Description

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.

Time Frame

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)

Title

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

Description

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.

Time Frame

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 Outcome Measure Information:

Title

Testosterone serum concentrations - Peak serum testosterone Concentration (Cmax)

Description

Testosterone serum concentrations after 200mg dose of DITEST in the fed and fasted states, as measured by the primary PK parameter of Cmax.

Time Frame

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)

Title

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

Description

Testosterone serum concentrations after 200mg dose of DITEST in the fed and fasted states, as measured by the primary PK parameter of AUC (0-10)

Time Frame

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)

Title

Adverse events

Description

Adverse events (AEs) observed throughout the study.

Time Frame

Through study completion - a maximum of 84 days.

Title

Vital signs

Description

Observed changes in vital signs data during the course of the study.

Time Frame

Through study completion - a maximum of 84 days.

Title

Electrocardiogram (ECG)

Description

Observed changes in ECG data during the course of the study.

Time Frame

Through study completion - a maximum of 84 days.

Title

Safety Laboratory Data

Description

Observed changes in Safety Laboratory data during the course of the study.

Time Frame

Through study completion - a maximum of 84 days.

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. Participation in another clinical trial or an investigation or licensed drug or device within the 3 months prior to inclusion in this study. 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

J Newell-Price, MA, PhD

Organizational Affiliation

University of Sheffield

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sheffield Teaching Hospital - Royal Hallamshire Hospital

City

Sheffield

State/Province

England

ZIP/Postal Code

S10 2JF

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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