Efficacy and Safety of Fispemifene in the Treatment of Hypogonadal Men With Chronic Obstructive Pulmonary Disease That Are on Oral Glucocorticoid Therapy

Inclusion criteria

• The subject has signed a written informed consent to participate in the study and has agreed to follow dosing instructions and complete all required study visits.
• The subject has COPD as defined by post-bronchodilator FEV1/FVC <0.7 as measured at screening.
• The subject is on a stable dose of oral glucocorticoids (dose has not changed in the past 3 months and is not anticipated to change during the subject's participation in the study)
• The subject is a male ≥20 years of age at the time of randomization.
• The subject has a screening total testosterone level and a confirmatory baseline total testosterone level ≤ 350 ng/dl. Testosterone levels should be determined from early morning (0700h to 0900h) specimens.
• The subject has a serum LH level of 1.7-15.0 IU/L and an FSH level of 1.5-15.0 IU/L at the screening visit.

Exclusion criteria

• Subject has elevated prolactin. (≥21.5 ng/mL or above upper limit of reference lab range)
• Subject has evidence of Benign Prostatic Hypertrophy (BPH) with obstructive symptoms as indicated by an International Prostate Symptom Score (IPSS) of ≥15.
• Subject has a history of or current breast cancer, prostate cancer, abnormal DRE (with suspicion of malignancy) or elevated PSA (>4 ng/ml ) or any other malignancy. History of basal cell carcinoma is allowed.
• Subject has a clinically significant endocrine or metabolic disease (e.g. thyroid disease, type I diabetes, severe hyperlipidemia). Severe hyperlipidemia is defined as total cholesterol >300 mg/dL or triglycerides >400 mg/dL. Type II diabetes is allowed only when HbAlc level is less than 8%.
• Subject has clinically significant cardiovascular disease, or abnormal findings on the baseline ECG, other than those related to COPD.
• Subject has systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥85 mmHg.
• Subject has significant polycythemia. (Hemoglobin >17.5 gm/dL or above upper limit of reference lab range)
• Subject has current or history of severe renal or hepatic impairment.
• Subject has current or history of thromboembolic or blood coagulation disorder.
• Subject has current or history of cerebrovascular incident (e.g. bleeding, stroke or transient ischemic attack).
• Subject has clinically relevant abnormal findings in any safety laboratory tests including liver enzymes (ALT, AST) more than 1.5 times the upper limit of normal for the testing laboratory or creatinine >1.4 mg/dl .
• Subject is heterozygous or homozygous for Factor V Leiden.
• Subject has clinically significant abnormal findings at physical examination other than those related to COPD.
• Subject has used transdermal testosterone therapy within 14 days or intramuscular testosterone therapy within 30 days prior to screening blood draw.
• Subject has used any form of hormone therapy affecting estrogen and/or androgen metabolism within 30 days prior to screening blood draw.
• Subject has used any other injectable hormonal therapy (e.g. luteinizing hormone releasing hormone (LHRH)-antagonist or- agonist, growth hormone (GH) therapy) within 30 days prior to screening blood draw.
• Subject has used any other medication affecting the Hypothalamic-Pituitary-Gonadal (HPG)-axis within 30 days prior to screening blood draw.
• Subject has used any dietary supplements and/or herbal therapies affecting estrogen and/or testosterone metabolism or the HPG axis within 30 days prior to screening blood draw.
• Subject is using potent inhibitors of CYP3A4 (e.g. ketoconazole, ritonavir, etc) on Day 1 or intends to use these medications during the study.
• Subject is using potent inducers of CYP3A4 on Randomization Day 1or intends to use these medications during the study.
• Subject is using medication metabolized by CYP2B6, CYP2C9, CYP2C19 and CYP3A4 and having a narrow therapeutic index on Day 1 or intends to use these medications during the study
• Subject consumes more than 14 drinks containing alcohol per week. (One drink = 1.5 oz. of distilled spirits, or 12 oz. of beer, or 5 oz. of wine.).
• Subject has a history of or current drug abuse within 6 months prior to screening visit.
• Subject currently has untreated sleep apnea.
• Subject has been a participant in another clinical intervention study within 30 days prior to the planned randomization on Day 1.
• Subject has any physical or mental condition, which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
• Subject has previously participated in this study or any other clinical study of fispemifene.