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

NCT02369796 | Terminated Phase 2 Results DMC

• 4 other identifiers: TAK-448-2001U1111-1162-48922014-002155-2514/LO/1950
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hypogonadotropic Hypogonadism

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (8)

• Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups

  Area under the pharmacodynamic (PD) total serum testosterone (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 22 pre-dose and multiple time points (up to 72 hours) post dose

• Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Twice Weekly Dosing Groups

  Area under the 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 pre-dose and multiple time points (up to 72 hours) post dose

• Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups

  Area under the 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 22 pre-dose and multiple time points (up to 72 hours) post dose

• Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Twice Weekly Dosing Groups

  Area under the 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 pre-dose and multiple time points (up to 72 hours) post dose

• Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups

  Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose.

  Day 22 pre-dose

• Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Twice Weekly Dosing Group

  Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose.

  Day 25 pre-dose

• Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups

  Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose.

  Day 22 pre-dose

• Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Twice Weekly Dosing Groups

  Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose.

  Day 25 pre-dose

Secondary Outcomes (4)

• Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F)

  Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose

• AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F

  Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose

• AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F

  Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose

• Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F

  Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose

Study Arms (5)

TAK-448 3 µg once weekly

EXPERIMENTAL

TAK-448 3 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22.

Drug: TAK-448

TAK-448 1 µg once weekly

EXPERIMENTAL

TAK-448 1 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22.

Drug: TAK-448

TAK-448 0.3 µg once weekly

EXPERIMENTAL

TAK-448 0.3 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22.

Drug: TAK-448

TAK-448 0.3 µg twice weekly

EXPERIMENTAL

TAK-448 0.3 µg, subcutaneous injection, twice weekly on Days 1, 4, 8, 11, 15, 18, 22, and 25.

Drug: TAK-448

TAK-448 0.1 µg twice weekly

EXPERIMENTAL

TAK-448 0.1 µg, subcutaneous injection, twice weekly on Days 1, 4, 8, 11, 15, 18, 22, and 25.

Drug: TAK-448

Interventions

TAK-448 DRUG

TAK-448 solution for subcutaneous injection

TAK-448 0.1 µg twice weekly; TAK-448 0.3 µg once weekly; TAK-448 0.3 µg twice weekly; TAK-448 1 µg once weekly; TAK-448 3 µg once weekly

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• 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.
• The participant has two morning total serum testosterone (ST) concentrations ≤12.0 nmol/L (≤3.46 ng/mL) taken during the Screening period.
• Is male and aged 18 to 60 years, inclusive.
• Has a body mass index (BMI) between 25.0 and 50.0 kg/m\^2, inclusive.
• If diagnosed with type II diabetes mellitus (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).
• Has a luteinizing hormone (LH) concentration \<8 IU/L at Screening.
• 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.

You may not qualify if:

• Has received any investigational compound within 30 days prior to Screening.
• Has received TAK-448 in a previous clinical study, or previous cohort.
• 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.
• 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.
• 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.
• Has a history of hypersensitivity or allergies to any component of the formulation of TAK-448.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to Screening.
• Is required to take excluded medications, supplements, or food products.
• Intends to donate sperm during the course of this study or for 12 weeks after the last dose of study drug.
• Has clinical evidence of anatomic or pathological hypothalamic/pituitary disease.
• 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.
• 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.
• Has a history of or present prostate disease (including benign prostatic hyperplasia) or prostate-specific antigen (PSA) is \>4 ng/mL at Screening.
• Has a known history of human immunodeficiency virus infection at Screening.
• Is deemed by the study team to have poor peripheral venous access.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Hypogonadism

Interventions

metastin (46-54), acetyl-tyrosyl(46)-hydroxypropyl(47)-threonyl(49)-azaglycyl(51)-methylarginyl(53)-tryptophyl(54)-

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 17, 2015
• First Posted: February 24, 2015
• Study Start: February 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 31, 2017
• Results First Posted: March 31, 2017

Record last verified: 2017-02

Locations

GB (1)