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

Takeda

Status and phase: Terminated; Phase 2

Conditions: Low Testosterone

Treatments: Drug: TAK-448; Drug: TAK-448 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02381288

U1111-1150-2776 (Registry Identifier)

TAK-448-2002

Details and patient eligibility

About

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.

Full description

The drug tested in this study is called TAK-448. TAK-448 was 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 looked at ST levels in men who took TAK-448.

The study enrolled 17 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of the following treatment groups-which remained undisclosed to the participants and study doctor during the study (unless there is an urgent medical need):

• TAK-448 0.1 µg
• TAK-448 0.3 µg
• TAK-448 1.0 µg
• Placebo (dummy inactive injection) - this was a injection that looks like the study drug but has no active ingredient All participants received subcutaneous injection either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.

This single-center trial was conducted in the United States. The overall time to participate in this study is up to 56 days. Participants made daily visits to the clinic for 8 weeks, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Enrollment: 17 patients

Sex: Male

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has total serum testosterone (ST) levels less than 300 ng/dL at Screening.
2. Has a body mass index (BMI) between 20.0 and 40.0 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 >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, glycosylated hemoglobin (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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17 participants in 4 patient groups, including a placebo group

TAK-448 0.1 mcg

Experimental group

Description:

TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.

Treatment:

Drug: TAK-448

TAK-448 0.3 mcg

Experimental group

Description:

TAK-448 0.3 mcg, injection, subcutaneously, twice-weekly on Days 1 through 39.

Treatment:

Drug: TAK-448

TAK-448 1.0 mcg

Experimental group

Description:

TAK-448 1.0 mcg, injection, subcutaneously, once-weekly on Days 1 through 36.

Treatment:

Drug: TAK-448

Placebo

Placebo Comparator group

Description:

TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.

Treatment:

Drug: TAK-448

Drug: TAK-448 Placebo