Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-GDC-9545 Following a Single Oral Dose (Part 1) and to Evaluate the Absolute and Relative Bioavailability of Oral Capsule Formulations of GDC-9545 (Part 2) in Healthy Female Subjects of Non-Childbearing Potential
Condition: Healthy Volunteers
Intervention: [14C]-GDC-9545; GDC-9545 Solution for Infusion; GDC-9545/F12 Capsule; GDC-9545/F18 Capsule
Intervention description: Participants will receive a single oral dose of [14C]-GDC-9545 capsule, 30 milligrams (mg) (not more than [NMT] 4.6 megabecquerel [MBq]; 124 microcurie [μCi]) with approximately 240 millilitres (mL) water in the fasted state.; Treatment B: 30 mg GDC-9545 as a solution for infusion, 3 mg/mL administered intravenously (IV) in 10 mL as an infusion over 30 minutes.; Treatment C: GDC-9545/F12 capsule, 30 mg, administered orally with approximately 240 mL water.; Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Female
Minimum age: 30 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is an open-label, single-center, two part study in healthy female subjects of
      non-childbearing potential to investigate the absorption, metabolism, and excretion of
      [14C]-GDC-9545 (Part 1), the absolute bioavailability of formulations F12 and F18 (i.e.,
      GDC-9545/F12 capsule, 30 mg and GDC-9545/F18 capsule, 30 mg) and relative bioavailability of
      GDC-9545 oral capsule F18 to the F12 formulation (Part 2). It is planned that Part 1 will
      begin prior to Part 2 of the study, and that the two parts of the study will partially
      overlap.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy female subjects of non-childbearing potential that are non-pregnant,
             non-lactating females, who are either postmenopausal or surgically sterile, aged 30 to
             65 years, inclusive, at time of signing the Informed Consent Form (ICF)

          -  A body mass index (BMI) between 18.5 and 32.0 kg/m^2, inclusive, at screening

          -  Ability to comply with the study protocol

          -  Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools
             per day) (Part 1 only)

        Exclusion Criteria:

          -  Women of childbearing potential, women who are pregnant or breastfeeding

          -  Subjects who have received any investigational medicinal product (IMP) in a clinical
             research study within the 90 days prior to Day 1 (Part 1) or Day 1 of Period 1 (Part
             2)

          -  History of serious adverse reaction or serious hypersensitivity to any drug or allergy
             to the study drug formulation excipients

          -  Subjects who are, or are immediate family members of, a study site or Sponsor employee

          -  Subjects who have previously been administered IMP in this study. Subjects who have
             taken part in Part 1 are not permitted to take part in Part 2.

          -  Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; i.e.,
             the virus that causes COVID-19) infection

          -  Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or
             human immunodeficiency virus (HIV) antibody at screening

          -  History of any drug or alcohol abuse in the past 2 years

          -  Regular alcohol consumption >14 units per week

          -  A confirmed positive alcohol breath test at screening or admission

          -  Current smokers and those who have smoked within the last 12 months

          -  Current users of e-cigarettes and nicotine replacement products and those who have
             used these products within the last 12 months

          -  Confirmed positive drugs of abuse test result at screening or admission

          -  Radiation exposure, including that from the present study, excluding background
             radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv
             in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker,
             as defined in the Ionising Radiation Regulations 2017, shall participate in the study
             (Part 1 only)

          -  Subjects who do not have suitable veins for multiple venipunctures/cannulation as
             assessed by the Investigator or delegate at screening

          -  Clinically significant abnormal clinical chemistry, hematology, coagulation or
             urinalysis as judged by the Investigator

          -  Evidence of renal impairment at screening, as indicated by an estimated creatinine
             clearance (CLcr) of <70 mL/min using the Cockcroft-Gault equation

          -  History of clinically significant cardiovascular, renal, hepatic, dermatological,
             chronic respiratory or gastrointestinal (GI) disease (especially peptic ulceration, GI
             bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome),
             neurological or psychiatric disorder, as judged by the Investigator

          -  Presence or history of clinically significant allergy requiring treatment, as judged
             by the Investigator

          -  Donation of blood or plasma within the previous 3 months or loss of greater than 400
             mL of blood

          -  Subjects who are taking, or have taken, any medication (e.g., prescription drugs,
             over-the-counter drugs, hormone replacement therapy [HRT], vaccines, topical
             medications, herbal or homeopathic remedies, nutritional supplements), other than up
             to 4 g of paracetamol per day, in the 14 days before IMP administration. Exceptions
             may apply on a case by case basis, if considered not to interfere with the objectives
             of the study, as determined by the Investigator.

          -  Subjects who are taking, or have taken, oral antibiotics within 4 weeks or IV
             antibiotics within 8 weeks prior to admission

          -  Subjects who are taking, or have taken, any medications/products known to alter drug
             absorption, metabolism, or elimination processes, including St. John's wort, within 30
             days prior to admission

          -  History of GI surgery (with the exception of appendectomy unless it was performed
             within the previous 12 months) (Part 1 only)

          -  Acute diarrhea or constipation in the 7 days before the predicted Day 1. If screening
             occurs >7 days before the Day 1, this criterion will be determined on Day 1. Diarrhea
             will be defined as the passage of liquid feces and/or a stool frequency of greater
             than 3 times per day. Constipation will be defined as a failure to open the bowels for
             3 days (Part 1 only)

          -  Malabsorption syndrome or other condition that would interfere with enteral absorption

          -  History or presence of an abnormal ECG that is clinically significant in the
             Investigator's opinion, including complete left bundle branch block, second- or
             third-degree atrioventricular heart block, or evidence of prior myocardial infarction

          -  QT interval corrected through use of Fridericia's formula (QTcF) >440 msec
             demonstrated by at least two ECGs >30 minutes apart

          -  History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such
             as structural heart disease (e.g., severe left ventricular systolic dysfunction, left
             ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia
             demonstrated by diagnostic testing), clinically significant electrolyte abnormalities
             (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden
             unexplained death or long QT syndrome

          -  Confirmed (e.g., 2 consecutive measurements) baseline heart rate ≤50 bpm prior to
             enrollment

          -  Current treatment with medications that are well known to prolong the QT interval

          -  Absolute neutrophil count <1.3 x 10^9/L (1300/μL)

          -  Failure to satisfy the Investigator of fitness to participate for any other reason