A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism
Condition: Hypogonadotropic Hypogonadism
MeSH terms: Hypogonadism
Intervention: TAK-448
Intervention description: TAK-448 solution for subcutaneous injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: Male
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Drug therapy

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.
    

Eligibility criteria:

        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 serum testosterone (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 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).

          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) electrocardiogram (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.