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

NCT02381288 | Terminated Phase 2 Results DMC

• 2 other identifiers: TAK-448-2002U1111-1150-2776
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Low Testosterone

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• 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-daily regimen Day 42; Twice-weekly regimen Day 39; Once-weekly regimen Day 36

• Trough Serum Concentration (Ctrough) of ST

  Trough serum concentration of total and free ST, defined as lowest Baseline concentration.

  Once-daily regimen Day 42; Twice-weekly regimen Day 39; Once-weekly regimen Day 36

Secondary Outcomes (4)

• Serum Testosterone Cmax: Maximum Observed Plasma Concentration

  Day 1 (first dose) and Day 42 for once-daily regimen, Day 39 for twice-weekly regimen, or Day 36 for once-weekly regimen (last dose)

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

  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.

• AUCt: Area Under the Plasma Concentration-Time Curve for TAK-448F

  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.

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

  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.

Study Arms (4)

TAK-448 0.1 mcg

EXPERIMENTAL

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

Drug: TAK-448

TAK-448 0.3 mcg

EXPERIMENTAL

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

Drug: TAK-448

TAK-448 1.0 mcg

EXPERIMENTAL

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

Drug: TAK-448

Placebo

PLACEBO COMPARATOR

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.

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

Interventions

TAK-448 DRUG

TAK-448 solution for subcutaneous injection

Placebo; TAK-448 0.1 mcg; TAK-448 0.3 mcg; TAK-448 1.0 mcg

TAK-448 Placebo DRUG

TAK-448 placebo-matching solution for subcutaneous injection

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has total serum testosterone (ST) levels less than 300 ng/dL at Screening.
• Has a body mass index (BMI) between 20.0 and 40.0 kg/m\^2, inclusive at Screening.
• 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.

You may not qualify if:

• 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:
• Has a serum creatinine \>2.0 milligrams per deciliter (mg/dL) at Screening.
• Is receiving dialysis treatment.
• 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.
• Has thyrotropin (TSH) levels less than (\<) 0.3 or \>7.5 milli-international units per liter (mIU/L) at Screening.
• 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.
• Has luteinizing hormone (LH) \>9.4 units per liter (U/L) at Screening.
• Is receiving insulin therapy.
• Has a hematocrit \<30 percent (%) or \>48% at Screening.
• Has a glycosylated hemoglobin (HbA1c) \>8.0 at Screening (Cohort 1).
• 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).
• 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.
• Has used gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, antiandrogens, clomiphene, or other reproductive hormone-related agents within 6 months prior to Screening.
• Has used anabolic therapies (testosterone, dehydroepiandrosterone \[DHEA\], androstendione, any other androgen, or recombinant human growth hormone) within 1 year of Screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Boston, Massachusetts, United States

Location

MeSH Terms

Interventions

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

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: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: September 10, 2015
• Primary Completion: April 8, 2016
• Study Completion: April 8, 2016
• Last Updated: May 17, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-04

Locations

US (1)