Phase I trial to evaluate the safety and tolerability of GDC-0214 in healthy volunteers and patients with mild asthma
- Conditions
- AsthmaRespiratory - Asthma
- Registration Number
- ACTRN12617001227381
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 102
Key Inclusion Criteria for Healthy Volunteers • Signed Informed Consent Form
• Age 18-65 years
• Body mass index of 18-37 kg/m2
• Weight of 50-120 kg
• In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs.
• First forced expiratory volume (FEV1) >70 % predicted
• Forced vital capacity (FVC) >2.0 L
• Ability to demonstrate sufficient inspiratory effort using the inhaler training
• Ability to comply with the study protocol, including all study procedures
• Agreement to remain abstinent or use contraceptive methods
Key Inclusion Criteria for Patients with Mild Asthma • Signed Informed Consent Form
• Age 18-65 years
• Body mass index of 18-37 kg/m2
• Weight of 50-120 kg
• Documented physician-diagnosed mild asthma for at least 6 months prior to screening, defined as: Asthma that is controlled with as-needed reliever medication with or without a leukotriene receptor antagonist
• No use of inhaled corticosteroids within 60 days prior to initiation of study drug
• FeNO >40 ppb at screening and at pre-randomization visit
• No clinically significant ECG abnormalities
• Clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the investigator and Sponsor.
• FEV1 >70 % predicted
• FVC >2.0 L
• Ability to demonstrate sufficient inspiratory effort using the inhaler training device
• Ability to comply with the study protocol, including all study procedures
• Agreement to remain abstinent or use contraceptive methods
Key Exclusion Criteria for Healthy Volunteers
Subjects who meet any of the following criteria will be excluded from Parts A and B:
• History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, gastrointestinal, urologic, neurologic, or psychiatric disorders, in the investigator’s judgment
• History of nasal polyposis or nasal polyps identified during screening physical examination
• History of anaphylaxis, hypersensitivity, or significant drug allergies
• History of severe hypersensitivity to milk proteins
• History or presence of an abnormal ECG that is clinically significant
• Any medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the subject’s safe participation in and completion of the study
• Illicit drug or alcohol abuse within 12 months prior to initiation of study drug
• Positive alcohol screen at screening or pre-randomization
• Recent history of smoking within the 35 days prior to initiation of study drug
• Smokers not able to pass the tobacco-related screening and who cannot refrain from smoking during the study
• Positive urine test for selected drugs of abuse at screening
• Pregnant or breastfeeding, or intending to become pregnant during the study
Women of childbearing potential must have a negative pregnancy test result at screening or pre-randomization.
• Use of any prescription medications and products within 7 days prior to initiation of study drug and throughout the study
• Use of a investigational drug or recent participation in an investigational study
• Positive for hepatitis panel at screening
Exclusion Criteria for Patients with Mild Asthma
Subjects who meet any of the following criteria will be excluded from Part C:
• Any of the exclusion criteria for healthy volunteers above
• Lack of asthma control defined as respiratory symptoms requiring use of a reliever inhaler (e.g., 2 puffs of SABA) more than twice a day on a regular basis within 4 weeks prior to initiation of study drug (not including reliever medication used to prevent symptoms)
• Recent asthma exacerbation requiring oral corticosteroid use or urgent medical care for asthma within 12 weeks prior to initiation of study drug
• Any asthma-related history, symptoms, or findings that precludes the subject’s safe participation in and completion of the study in the investigator’s judgment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective of this study is to characterize the safety profile associated with GDC-0214. This will be measured through observation and the severity of any adverse events, change from baseline in vital signs, and laboratory test results[Adverse events will be reported after any occurrence after the first dose. Vital signs will be collected at each study visit for part A (visit days 1 through 15). For part B and C they will be collected on visit days (1-17, 21, 28, 35 and 42). ]
- Secondary Outcome Measures
Name Time Method To characterize the PK profile of GDC 0214, Plasma concentrations of GDC-0214 will be assessed and pharmacokinetic parameters such as through AUC, tmax, Cmax, and half-life will be calculated.[To characterize the PK profile of GDC 0214 16 plasma samples will be assessed for GDC-0214 concentrations during the course of the SAD in order to sufficiently characterize PK parameters such as Tmax, Cmax,t1/2, and AUC. Individual PK parameters will not be assessed at specific time points since they require the totality of the data. PK will be collected on Day 1 (Pre-dose, 5 min (0.08h), 0.25h, 0.5h, 1h, 2h, 4h, 8h, and 12h). On Day 2 (24h and 36h post-dose). On Day 3 (48hr post-dose). On Day 4 (72h post-dose) and anytime during visit days 6, 10 and 15.]