A Study of the Safety, Tolerability, Pharmacokinetics and... | NCT03381144

ID	Type	Description	Link
2017-003498-33	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: GDC-0334	Experimental	Participants in up to 7 cohorts will receive single, ascending doses of GDC-0334 under fasting conditions.	Drug: GDC-0334
Part 1: Placebo	Placebo Comparator	Participants in up to 7 cohorts will receive single doses of placebo under fasting conditions.	Drug: Placebo
Part 2: GDC-0334	Experimental	Participants in up to 3 cohorts will receive single doses of GDC-0334 under fasting or fed conditions.	Drug: GDC-0334
Part 2: Placebo	Placebo Comparator	Participants in up to 3 cohorts will receive single doses of placebo under fasting or fed conditions.	Drug: Placebo
Part 3: GDC-0334	Experimental	Participants in up to 4 cohorts will receive multiple, ascending doses of GDC-0334 under fasting or fed conditions.	Drug: GDC-0334
Part 3: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GDC-0334	Drug	Part 1: GDC-0334 given orally with dose escalation between cohorts, based on emerging safety and pharmacokinetic (PK) data. Parts 2 and 3: doses to be based on the safety, tolerability, and PK data generated in the study. The dosing duration in Part 3 is planned to be at least 14 days, but no longer than 28 days.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants with Adverse Events		From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days)
Severity of Adverse Events, as Graded per the World Health Organization (WHO) Toxicity Grading Scale		From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days)
Change from Baseline in Blood Pressure		Up to approximately 42 days
Change from Baseline in Heart Rate		Up to approximately 42 days
Incidence of Electrocardiogram (ECG) Abnormalities		Up to approximately 42 days
Incidence of Clinical Laboratory Abnormalities		Up to approximately 30 days
Incidence of Physical Examination Abnormalities		Up to approximately 42 days
Incidence of Neurological Examination Abnormalities		Up to approximately 31 days
Columbia-Suicide Severity Rating Scale (C-SSRS) - Part 3 Only		Up to approximately 42 days

Secondary Outcomes

Measure	Description	Time Frame
Elapsed Time from Dosing at Which GDC-0334 is First Quantifiable in a Concentration versus Time profile (Tlag )		Up to approximately 35 days
Time to Maximum Plasma Concentration (Tmax) for GDC-0334		Up to approximately 35 days

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy males or non-pregnant, non-lactating healthy females. Females may be of non-childbearing potential or childbearing potential. Healthy females of childbearing potential must agree to use a highly effective method of contraception.
Healthy males must agree to use an adequate method of contraception
Body mass index of 18.0 to 32.0 kilograms per meter squared (kg/m^2) or, if outside the range, considered not clinically significant by the investigator
Must be willing and able to communicate and participate in the whole study

Exclusion Criteria:

Participants who have received any investigational medicinal product in a clinical research study within the previous 3 months
Participants who are study site employees, or immediate family members of a study site or sponsor employee
Participants who have previously been enrolled in this study. Participants who have enrolled in Part 1 are not permitted to enrol in Parts 2 or 3, and participants who have enrolled in Part 2 are not permitted to enroll in Part 3
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption >14 units per week (1 unit = ½ pint beer, 25 milliliters (mL) of 40% spirit or a 125-mL glass of wine)
Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 6 parts per million (ppm) at screening or admission
Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator
Positive drugs-of-abuse test result at screening or admission
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <70 milliliters per minute (mL/min) using the Cockcroft-Gault equation
History of seizure
History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder, as judged by the investigator
Participants with a history of cholecystectomy or gall stones (applies to any regimen where food effect is being explored)
History of serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Presence or history of active allergy requiring treatment, as judged by the investigator. History of hayfever is allowed unless it is active.
Donation or loss of greater than 400 mL of blood within the previous 3 months
Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days or 5 half-lives, whichever is longer, before investigational medicinal product administration. Exceptions may apply on a case-by-case basis, if considered not to interfere with the objectives of the study, as agreed by the principal investigator and sponsor's medical monitor.
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction, at screening or admission
QT interval corrected using Fridericia's formula (QTcF) > 450 milliseconds (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, coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
Current treatment with medications that are well known to prolong the QT interval
History of dermatographism
Presence or history of clinically significant skin disorders, as judged by the investigator (Parts 1 and 3 only)
History of trauma or surgery (laceration repair is not excluded) to the arm but not including wrist or hand injury/surgery (Parts 1 and 3 only)
Failure to satisfy the investigator of fitness to participate for any other reason