A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism

Hypogonadotropic Hypogonadism Clinical Trial

Official title:

An Open-Label, Phase 2a Study to Evaluate the Pharmacodynamics of Different Dosing Regimens of TAK-448, a Kisspeptin Agonist, in Male Overweight/Obese Participants With Hypogonadotropic Hypogonadism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02369796
• Other study ID #: TAK-448-2001
• Secondary ID: U1111-1162-48922
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2015
• Last updated: April 4, 2016
• Start date: February 2015
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effects on serum testosterone after 4 weeks of subcutaneous dose administration, with different doses and dosing frequencies of TAK-448 to overweight/obese males with hypogonadotropic hypogonadism (HH).

Description:

The drug being tested in this study is called TAK-448. TAK-448 is being tested to treat overweight/obese males with hypogonadotropic hypogonadism. This study will look at the effects of TAK-448 at different doses and different dosing frequencies on serum testosterone.

The study will enroll approximately 48 patients. There will be 6 cohorts and participants will be assigned to cohorts in sequential order. Cohort 1 will receive TAK-448 3 micrograms (µg) subcutaneously (SC) once weekly for 4 weeks. The dose for Cohorts 2 and 3 will be determined based on results from Cohort 1. Cohorts 2 and 3 will receive TAK-448 once weekly for 4 weeks or twice weekly for 4 weeks. The TAK-448 dose and dosing frequency for Cohorts 4, 5 and 6 will be determined based on results from Cohorts 1, 2 and 3.

All participants will be administered study drug via SC injection once or twice a week depending on their assigned cohort.

This single-centre trial will be conducted in the United Kingdom. The overall time to participate in this study is up to 12 weeks. Participants will make 8 to 12 visits to the clinic (depending once-weekly or twice-weekly dosing), and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. The participant has two morning total ST concentrations =12.0 nmol/L (=3.46 ng/mL) taken during the Screening period.

4. Is male and aged 18 to 60 years, inclusive.

5. Has a body mass index (BMI) between 25.0 and 50.0 kg/m^2, inclusive.

6. If diagnosed with T2DM, has a glycosylated hemoglobin (HbA1c) concentration <12% at Screening and is on a stable dose of up to 4 diabetes therapies (including insulin and/or glucagon-like peptide-1 therapies).

7. Has a luteinizing hormone (LH) concentration <8 IU/L at Screening.

8. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.

2. Has received TAK-448 in a previous clinical study, or previous cohort.

3. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than T2DM, its complications and associated conditions), which may impact the ability of the participant to participate or potentially confound the study results.

5. Has a recent history or clinical manifestations of significant cardiovascular disease (CVD) - such as a history of myocardial infarction or stroke in the 6 months preceding the Screening visit or has untreated peripheral arterial disease.

6. Has a history of hypersensitivity or allergies to any component of the formulation of TAK-448.

7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to Screening.

8. Is required to take excluded medications, supplements, or food products.

9. Intends to donate sperm during the course of this study or for 12 weeks after the last dose of study drug.

10. Has clinical evidence of anatomic or pathological hypothalamic/pituitary disease.

11. Is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-448, or a similar drug in the same class that might interfere with the conduct of the study.

12. Has a history of cancer (including prostate cancer), with the exception of basal cell carcinoma which has been in remission for at least 5 years prior to Screening.

13. Has a history of or present prostate disease (including benign prostatic hyperplasia) or prostate-specific antigen (PSA) is >4 ng/mL at Screening.

14. Has a known history of human immunodeficiency virus infection at Screening.

15. Is deemed by the study team to have poor peripheral venous access.

16. Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to Screening, or is planning to donate blood for 12 weeks after the last dose of study medication.

17. Has a Screening or Day -1 abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator.

18. Has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2× the upper limits of normal (ULN).

19. The participant, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

20. Has had more than two severe hypoglycemic events (requiring third party assistance) within 6 months prior to the Screening Visit.

21. Has a diagnosis of type 1 diabetes mellitus.

22. Has a history of diabetic ketoacidosis.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadotropic Hypogonadism

Intervention

Drug:
• TAK-448
TAK-448 solution for subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Area Under the Effect Curve from Time 0 to 72 hours (AUEC72) of Total Serum Testosterone (ST)	Area under the pharmacodynamic (PD) total ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for Baseline profile and those obtained after first and last dose.	Baseline and Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing.	No
Primary	Percent Change from Baseline in Area Under the Effect Curve from Time 0 to 72 hours (AUEC72) of Free Serum Testosterone (ST)	Area under the pharmacodynamic (PD) free ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for Baseline profile and those obtained after first and last dose.	Baseline and Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing.	No
Primary	Trough Serum Concentration (Ctrough) of Total Serum Testosterone (ST)	Trough serum concentration of total ST, defined as lowest Baseline concentration compared to pre-dose of the last dose.	Baseline and Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing.	No
Primary	Trough Serum Concentration (Ctrough) of Free Serum Testosterone (ST)	Trough serum concentration of free ST, defined as lowest Baseline concentration compared to pre-dose of the last dose.	Baseline, Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing.	No
Secondary	Cmax: Maximum Observed Plasma Concentration for TAK-448F	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Once weekly dosing: Day 1 and Day 22 predose and at multiple timepoints (up to 8 hours) post-dose. Twice weekly dosing: Day 1 and Day 25 predose and at multiple timepoints (up to 8 hours) post-dose.	No
Secondary	AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-448F	AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.	Once weekly dosing: Day 1 and Day 22 predose and at multiple timepoints (up to 8 hours) post-dose. Twice weekly dosing: Day 1 and Day 25 predose and at multiple timepoints (up to 8 hours) post-dose.	No
Secondary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F	(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).	Once weekly dosing: Day 1 and Day 22 predose and at multiple timepoints (up to 8 hours) post-dose. Twice weekly dosing: Day 1 and Day 25 predose and at multiple timepoints (up to 8 hours) post-dose.	No
Secondary	Terminal Elimination Half-life (T1/2) for TAK-448F	Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.	Once weekly dosing: Day 1 and Day 22 predose and at multiple timepoints (up to 8 hours) post-dose. Twice weekly dosing: Day 1 and Day 25 predose and at multiple timepoints (up to 8 hours) post-dose.	No