Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone

Low Testosterone Clinical Trial

Official title:

A Randomized, Single-Blind, Placebo-Controlled Phase 2a Study to Evaluate the Stimulatory Effects of TAK-448, a Kisspeptin Analog, Administered Intermittently in Middle-aged and Older Men With Low Testosterone

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02381288
• Other study ID #: TAK-448-2002
• Secondary ID: U1111-1150-2776
• Status: Terminated
• Phase: Phase 2
• First received: March 2, 2015
• Last updated: February 2, 2017
• Start date: September 2015
• Est. completion date: November 2016

Study information

• Verified date: February 2017
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effects on serum testosterone (ST) after 6 weeks of subcutaneous (SC) administration of different doses and dosing frequencies of TAK-448 to middle-aged and older men with low ST levels.

Description:

The drug being tested in this study is called TAK-448. TAK-448 is being tested to define a dose and dose frequency which results in a clinically relevant improvement in ST in middle-aged and older men with low ST levels. This study will look at ST levels in men who take TAK-448.

The study will enroll approximately 66 participants. Two Cohorts are planned for this study. Cohort 1 will include 3 dose groups that will run in parallel and consist of the following SC doses, 0.1 mcg once-daily, 0.3 mcg twice-weekly, and 1.0 mcg once-weekly for a period of 6 weeks. Within each dose group in Cohort 1, 11 participants will be enrolled and assigned so that 8 will receive TAK-448 and 3 will receive placebo. Cohort 2 will be enrolled after the completion of Cohort 1 and may include up to 3 dose groups. The dose and dosing frequency will be decided based on results from Cohort 1.

This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 16 weeks. Participants will make daily visits to the clinic for 8 weeks, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Has total ST levels less than 300 nanograms per deciliter (ng/dL) at 2 separate time points during Screening.

2. Has a body mass index (BMI) between 20.0 and 40.0 kilogram per square meter (kg/m^2), inclusive at Screening.

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

Exclusion Criteria:

1. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality that may impact the ability of the participant to participate or potentially confound the study results. Participants will be excluded based on:

1. Has a serum creatinine greater than (>) 2.0 milligrams per deciliter (mg/dL) at Screening.

2. Is receiving dialysis treatment.

3. Has an American Urological Association (AUA)/ International Prostate Symptom Score (I-PSS) score of >19 or serum prostate-specific antigen (PSA) >4 nanogram per milliliter (ng/mL) at Screening.

4. Has thyrotropin (TSH) levels less than (<) 0.3 or >7.5 milli-international units per liter (mIU/L) at Screening.

5. Has systolic blood pressure >160 millimeter of mercury (mm Hg) or diastolic blood pressure >100 mm Hg (if out of range may be repeated once for eligibility determination) at Screening.

6. Has luteinizing hormone (LH) >9.4 units per liter (U/L) at Screening.

7. Is receiving insulin therapy.

8. Has a hematocrit <30 percent (%) or >48% at Screening.

9. Has a glycosylated hemoglobin (HbA1c) >8.0 at Screening (Cohort 1).

2. Has type 2 diabetes mellitus defined as fasting blood glucose >125 mg/dL, HbA1c >6.2%, or use of antidiabetic medication (Cohort 2 only).

3. Has clinical evidence of anatomic or pathological hypothalamic/pituitary/testicular disease, such as (but not limited to) Klinefelter's syndrome, Kallmann's syndrome, systemic infiltrative diseases (hemochromatosis, sarcoidosis, Wilson's disease), or prior pituitary surgery.

4. Has used gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, antiandrogens, clomiphene, or other reproductive hormone-related agents within 6 months prior to Screening.

5. Has used anabolic therapies (testosterone, dehydroepiandrosterone [DHEA], androstendione, any other androgen, or recombinant human growth hormone) within 1 year of Screening.

Related Conditions & MeSH terms

• Low Testosterone

Intervention

Drug:
• TAK-448
TAK-448 solution for subcutaneous injection
• TAK-448 Placebo
TAK-448 placebo-matching solution for subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Average Serum Concentration (Cav) of Total ST After 6 Weeks of Dosing	Cav is the average serum concentration of the dosing interval, calculated as area under the effect curve (AUEC) divided by the duration of the dosing interval.	Once-weekly Dosing Days 1, 22, 29 and 36, Twice-weekly Dosing Days 1, 22, 25, 29 and 39, and Daily Dosing Days 1, 22, 29 and 42, predose and at multiple time intervals (up to 168 hours) post-dose
Primary	Trough Serum Concentration (Ctrough) of ST From Day 22 to Day 43	Trough serum concentration of total and free ST, defined as lowest Baseline concentration compared to Day 22 and Day 43.	Once-weekly Dosing Days 1, 22, 29 and 36, Twice-weekly Dosing Days 1, 22, 25, 29 and 39, and Daily Dosing Days 1, 22, 29 and 42, predose and at multiple time intervals (up to 168 hours) post-dose
Secondary	Serum Testosterone Cmax: Maximum Observed Plasma Concentration	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. It is evaluated after doses on Day 1 (first dose) and last dose (Day 42 for once-daily, Day 39 for twice-weekly, or Day 36 for once-weekly dosing).	Once-weekly Dosing Days 1, 22, 29 and 36, Twice-weekly Dosing Days 1, 22, 25, 29 and 39, and Daily Dosing Days 1, 22, 29 and 42, predose and at multiple time intervals (up to 168 hours) post-dose
Secondary	Cmax: Maximum Observed Plasma Concentration for the Free Form of TAK-448 (TAK-448F)	Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. It is evaluated after doses on Day 1 (first dose) and last dose (Day 42 for once-daily, Day 39 for twice-weekly, or Day 36 for once-weekly dosing).	Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.
Secondary	AUCt: Area Under the Plasma Concentration-Time Curve for TAK-448F	Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. It is evaluated after doses on Day 1 (first dose) and last dose (Day 42 for once-daily, Day 39 for twice-weekly, or Day 36 for once-weekly dosing).	Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.
Secondary	Terminal Elimination Half-life (T1/2) for TAK-448F	T1/2 is the time required for half of the drug to be eliminated from the plasma. It is evaluated after doses on Day 1 (first dose) and last dose (Day 42 for once-daily, Day 39 for twice-weekly, or Day 36 for once-weekly dosing).	Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.