Overview
The purpose of this study is to evaluate the effects of single and multiple doses of ABCL635 administered by subcutaneous (SC) injection to healthy men and to postmenopausal women with or without any vasomotor symptoms (VMS) or hot flashes, and to postmenopausal women with moderate-to-severe VMS associated with menopause. The safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters of ABCL635 will be assessed in all study participants; the effects on frequency and severity of VMS will be assessed in postmenopausal women who experience moderate-to-severe symptoms.
Description
The study consists of 3 parts. In Part A, single ascending doses (SAD) of ABCL635 or placebo will be administered to healthy male and female participants. In Part B, up to 3 multiple ascending doses (MAD) of ABCL635 or placebo will be administered to healthy postmenopausal women with or without VMS. In Part C, a single dose of ABCL635 or placebo will be administered to postmenopausal women experiencing moderate-to-severe VMS associated with menopause. Part C participants receiving placebo will be offered to participate in an open label extension (OLE) cohort and receive a single dose of ABCL635 upon completion of a 12-week assessment.
Eligibility
Inclusion Criteria:
- Good general health as determined through a review of their medical history and after conducting a general physical examination
- Body weight ≥ 45 to ≤ 120 kg
- Body mass index (BMI) between 18.5 kg/m2 and 35.0 kg/m2
- Non- or ex-smoker (an ex-smoker is defined as someone who completely stopped using nicotine products for at least 90 days prior to the first study drug administration)
- Healthy man or a postmenopausal woman who is ≥ 40 and ≤ 65 years of age OR a postmenopausal woman with or without VMS and who is ≥ 40 and ≤ 65 years of age OR a postmenopausal woman who is ≥ 40 and ≤ 65 years of age seeking treatment for relief for VMS
- If a woman:
- has been compliant with local and/or national guidelines for breast cancer screening with documentation of a mammogram with normal/negative or no clinically significant findings. A screening mammogram may be conducted during study screening period, if needed
- has spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L); or had a bilateral oophorectomy > 6 weeks prior to screening
- If a man:
- possess a testosterone concentration of ≥ 15 nmol/L at the time of screening
- can procreate and agree to use one of the acceptable contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration OR is unable to procreate; defined as surgically sterile
Exclusion Criteria:
- Pregnancy and/or lactation.
- History of abnormal uterine bleeding or endometrial hyperplasia.
- Previous or current history of a malignant tumor, except for basal cell carcinoma.
- Seated pulse rate less than 50 beats per minute (bpm) or more than 100 bpm or a seated blood pressure < 90/50 mmHg or > 140/90 mmHg
- eGFR < 60 mL/min/1.73 m2
- Severe hypersensitivity reactions (like angioedema) to any drugs.
- Significant uncontrolled cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease.
- Clinically significant ECG abnormalities
- Syncope or unexplained dizziness.
- Use of any medication (hormonal, prescription, over the counter, herbal, or natural) for the treatment of hot flashes or over-the-counter products (including supplements) containing testosterone less than 28 days prior to study drug administration