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A Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Single and Multiple Ascending Doses of GDC-0334 and the Effect of Food on the Pharmacokinetics of GDC-0334 in Healthy Adult Participants

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ClinicalTrials.gov Identifier: NCT03381144
Recruitment Status : Recruiting
First Posted : December 21, 2017
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
This is a randomized, double-blind, placebo-controlled, single-center, three-part study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of single and multiple ascending doses of GDC-0334 and the effect of food on the pharmacokinetics of GDC-0334 in healthy adult participants.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: GDC-0334 Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I, Randomised, Double-Blind, Placebo-Controlled, Single Centre, 3-Part, Study Designed to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Single and Multiple Ascending Doses of GDC-0334 and the Effect of Food on the Pharmacokinetics of GDC-0334 in Healthy Adult Subjects
Actual Study Start Date : December 8, 2017
Estimated Primary Completion Date : July 3, 2019
Estimated Study Completion Date : July 3, 2019

Arm Intervention/treatment
Experimental: Part 1: GDC-0334
Participants in up to 7 cohorts will receive single, ascending doses of GDC-0334 under fasting conditions.
Drug: GDC-0334
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.

Placebo Comparator: Part 1: Placebo
Participants in up to 7 cohorts will receive single doses of placebo under fasting conditions.
Drug: Placebo
Participants will receive GDC-0334-matching placebo.

Experimental: Part 2: GDC-0334
Participants in up to 3 cohorts will receive single doses of GDC-0334 under fasting or fed conditions.
Drug: GDC-0334
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.

Placebo Comparator: Part 2: Placebo
Participants in up to 3 cohorts will receive single doses of placebo under fasting or fed conditions.
Drug: Placebo
Participants will receive GDC-0334-matching placebo.

Experimental: Part 3: GDC-0334
Participants in up to 4 cohorts will receive multiple, ascending doses of GDC-0334 under fasting or fed conditions.
Drug: GDC-0334
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.

Placebo Comparator: Part 3: Placebo
Participants in up to 4 cohorts will receive multiple doses of placebo under fasting or fed conditions.
Drug: Placebo
Participants will receive GDC-0334-matching placebo.




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events [ Time Frame: From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days) ]
  2. Severity of Adverse Events, as Graded per the World Health Organization (WHO) Toxicity Grading Scale [ Time Frame: From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days) ]
  3. Change from Baseline in Blood Pressure [ Time Frame: Up to approximately 42 days ]
  4. Change from Baseline in Heart Rate [ Time Frame: Up to approximately 42 days ]
  5. Incidence of Electrocardiogram (ECG) Abnormalities [ Time Frame: Up to approximately 42 days ]
  6. Incidence of Clinical Laboratory Abnormalities [ Time Frame: Up to approximately 30 days ]
  7. Incidence of Physical Examination Abnormalities [ Time Frame: Up to approximately 42 days ]
  8. Incidence of Neurological Examination Abnormalities [ Time Frame: Up to approximately 31 days ]
  9. Columbia-Suicide Severity Rating Scale (C-SSRS) - Part 3 Only [ Time Frame: Up to approximately 42 days ]

Secondary Outcome Measures :
  1. Elapsed Time from Dosing at Which GDC-0334 is First Quantifiable in a Concentration versus Time profile (Tlag ) [ Time Frame: Up to approximately 35 days ]
  2. Time to Maximum Plasma Concentration (Tmax) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  3. Maximum Observed Plasma Concentration (Cmax) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  4. Concentration at 24 hours Post-dose (C24) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  5. Concentration at 12 hours Post-dose (C12) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  6. Area Under the Plasma Concentration Curve from Time Zero to the Last Measurable Concentration (AUC0-t) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  7. Area Under the Plasma Concentration Curve from Time Zero Extrapolated to Infinity (AUC0-inf) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  8. Percentage of AUC0-inf Accounted for by Extrapolation to Infinity (AUC%extrap) for GDC-0334 [ Time Frame: Up to approximately 35 days ]
  9. Apparent Terminal Elimination Half-Life (t1/2) for GDC-0334 [ Time Frame: Up to approximately 35 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03381144


Contacts
Contact: Reference Study ID: GB40223 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. only) global-roche-genentech-trials@gene.com

Locations
United Kingdom
Quotient Clinical Ltd, Clinical Research Unit Recruiting
Nottingham, United Kingdom, NG11 6JS
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03381144     History of Changes
Other Study ID Numbers: GB40223
2017-003498-33 ( EudraCT Number )
First Posted: December 21, 2017    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No