Cystic fibrosis (CF) Nutritional, Metabolic, Endocrine Cystic fibrosis
Conditions
Interventions
Participants will be randomised to receive a single oral dose of GDC-6988 or placebo twice daily for 14 days (from Day 1 to Day 14).
Participants will also receive a single oral dose of salbutamol tw
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form 2. Age 18-55 years at time of signing Informed Consent Form 3. Ability to comply with the study protocol 4. Body mass index of 18-32 kg/m² at screening 5. Body temperature of 35-37.5 degrees C at screening and at Day -1 6. Systolic blood pressure of 90 - 150 mmHg and diastolic blood pressure of 50-95 mmHg at screening and at Day -1. Blood pressure should be measured while the subject is in a seated position 7. Agreement to abstain from consumption of caffeine-containing foods and beverages from 72 hours prior to clinic check-in and during the residential stay at the clinic 8. Agreement to abstain from consumption of alcohol from 24 hours prior to clinic check-in and during the residential stay at the clinic 9. FEV1 >80% of predicted at screening and at Day -1 10. Forced vital capacity (FVC) >2.0L by spirometry at screening 11. Ability to demonstrate correct use of the Smart DPI (with placebo capsules) at Screening 12. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: 12.1. Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during treatment and for 28 days after the final dose of study drug 12.2. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (=12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. 12.3. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices 12.4. Hormonal contraceptive methods must be supplemented by a barrier method 12.5. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject 12.6. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception 12.7. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form 12.8. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: 12.9. With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during treatment and for 28 days after final dose of study drug to avoid exposing the embryo. Men must refrain from donating sperm during this same period 12.10. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing d
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 28 days after the final dose of study drug. Women of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result on Day -1. 2. Study site employee or immediate family member of a study site or Sponsor employee 3. Treatment with investigational therapy (or blinded comparator) within 90 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug 4. Treatment with any immunosuppressive medication within 28 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug 5. Treatment with an herbal or homeopathic remedy within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study drug 6. Treatment with any vaccine within 14 days prior to initiation of study drug or a scheduled vaccination during study period (through the follow-up/early termination visit) 7. Treatment with any other (not already described above) prescription or non-prescription medication or dietary supplement (products taken by mouth that contain dietary ingredients such as vitamins, minerals, amino acids, herbs or botanicals) within 14 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug, with the following exceptions: 7.1. Oral contraceptives and hormone-releasing intrauterine devices and hormone-replacement therapies 7.2. Acetaminophen or paracetamol at a dose of up to 2 g/day 8. Positive for TB during screening or within 3 months prior to screening, defined as a positive QuantiFERON®-TB Gold test (QFT) 9. Positive HIV test at screening 10. Positive hepatitis B surface antigen (HBsAg) test at screening 11. Positive hepatitis C virus (HCV) antibody test at screening, except in subjects who meet either of the following sets of criteria: 11.1. Subject has undetectable HCV RNA levels for 6 months after completion of HCV anti-viral treatment and a negative HCV RNA test at screening. 11.2. Subject has two negative HCV RNA tests taken at least 7 days apart during screening. 12. Substance abuse, in the investigator's judgment, within 12 months prior to screening, positive urine drug test at screening or Day -1, or positive breath alcohol test at screening or Day -1 13. Positive urine cotinine test at screening or Day -1 14. Use of illicit drugs or hallucinogenic substances (including marijuana) within 28 days prior to screening or on at least 30 days within 2 years prior to screening, or unwillingness to abstain from their use during the study 15. Use of tobacco or nicotine products within 28 days prior to screening or on at least 30 days within 2 years prior to screening, or unwillingness to abstain from their use during the study 16. Receipt of blood products within 120 days prior to screening 17. Hospitalization within 28 days prior to initiation of study drug 18. Anticipation of need for a surgical procedure during the study 19. Infection requiring oral or IV antibiotics within 28 days prior to screening or any evidence of current infection (e.g., bacterial, viral, fungal) 20. In the setting of a pandemic or epidemic, screening for active infections should be considered according to local or institutional guidelines or guidelines of applicable professional societies. 21. Upper or lower respiratory tract infection within 2 weeks prior to initiation of study drug 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence and severity of adverse events, with severity determined according to the Division of AIDS (DAIDS) toxicity grading scale assessed throughout the trial from screening until discharge from the study (approximately 10 weeks) 2. Incidence and severity of vital sign, laboratory test, spirometry, oscillometry, and ECG abnormalities assessed throughout the trial from screening until discharge from the study (approximately 10 weeks) 3. Incidence and severity of spirometry and oscillometry abnormalities after salbutamol (albuterol) pretreatment assessed throughout the trial from screening until discharge from the study (approximately 10 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Plasma concentration of GDC-6988 and relevant pharmacokinetic (PK) parameters measured from the first dose of GDC-6988 until discharge from the study (approximately 6 weeks) 2. Relationship between GDC-6988 exposure and safety endpoints assessed throughout the trial from the first dose of GDC-6988 until discharge from the study (approximately 6 weeks) | — |
Countries
England, United Kingdom
Contacts
Public ContactTrial Information Support Line (TISL)
Outcome results
None listed