A Study to Investigate the Safety, Tolerability, and Pharmacokinetics (PK) of Oral AZD6793 in Healthy and Chronic Obstructive Pulmonary Disease Participants, to Assess the Relative Oral Bioavailability Between Two Formulations, and the Food Effect on the PK of AZD6793 Compared to Fasting State.
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
The purpose of the study is to assess the safety and tolerability of AZD6793 suspension following oral administration of Single Ascending Dose (SAD) [Part 1] and Multiple Ascending Dose (MAD) [Part 2] in healthy participants.
Additionally, the study will include Part 3 (bioavailability and food effect cohort) to assess the relative oral bioavailability between test formulation and oral suspension (reference formulation) as well as the effect of a high fat high calorie (HFHC) meal on the PK of AZD6793 test formulation, in comparison to fasting conditions, after a single oral dose of AZD6793 in healthy participants.
Part 4 of the study (Chronic Obstructive Pulmonary Disease [COPD] cohort) is intended to evaluate AZD6793 safety, tolerability, and PK profile for the first time in participants with moderate to severe COPD.
Part 1 (SAD), Part 2 (MAD) and Part 3 (Bioavailability and food effect cohort) have been completed. Although it was planned that 5 cohorts would be included in Part 1, only 4 cohorts (32 participants) were included. Part 3 of the study was concluded with 13 healthy participants.
Full description
Parts 1, 2, and 3 were conducted in a single center and Part 4 is conducted in 2 centers.
Part 1 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2)
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 (the day before IMP administration [Day 1]) until at least 72 hours after IMP administration. Participants will then be discharged on Day 4 if in good health and after all samples have been collected. Depending on the emerging data, the length of the stay at the Clinical Unit may be changed.
- A Follow-up Visit within 6 ± 1 days after the IMP dose (this visit may be done later if indicated, for example, if emerging PK data indicates a longer AZD6793 half-life than was predicted).
Part 2 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2).
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 (the day before first IMP administration [Day 1]) until Day 10. participants will receive a single dose of IMP in the morning on Day 1. After a washout of at least 48 hours (depending on PK data from Part 1), participants will be dosed twice daily (12 hours apart) from Day 3 through Day 7. Participants will receive the last dose of IMP in the morning of Day 8. Participants will then be discharged on Day 10 if in good health and after all samples have been collected.
- A Follow-up Visit within 6 ± 1 days after the last IMP dose (this visit may be done later if indicated, for example, if emerging PK data indicates a longer AZD6793 half-life than was predicted).
Part 3 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2).
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 until Day 3. Participants will be randomised on Day 1 of Visit 3 to one of 3 treatment sequences and will receive AZD6793 on Day 1 of each treatment period. Dose administration will be separated by a washout period of at least 3 days from the previous IMP dose of each treatment period.
- A Follow-up Visit within 6 ± 1 days after the last IMP dose
Part 4 of the study will comprise:
- A Screening Period of maximum 35 days (Day -35 to -2)
- A Treatment Period of up to 28 days (at least 26 days) of dosing with AZD6793 or placebo. The participants will be admitted to the Clinical Unit on Day -1 and will receive single dose of AZD6793 or placebo on Day 1 and discharged from the Clinical Unit in the evening on Day 1 (12 hours post-dose).
- A Follow--up Visit 6 ± 2 days after the last IMP dose
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Main Inclusion Criteria:
Parts 1,2 and 3:
- Healthy male or female participants aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture
- Females must have a negative pregnancy test must not be lactating and must be either (a) non-childbearing potential, confirmed by post-menopausal defined as amenorrhea for at least 12 months; documentation of irreversible surgical sterilisation or (b) childbearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile (Must agree to use, with their partner, an approved method of highly effective contraception).
- Male participants and their female partners of childbearing potential must be willing to use highly effective contraception measures and male participants must refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
- Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg, at the Screening Visit.
Part 4:
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Male and/or female participants, who have moderate to severe COPD, and aged 40 through 80 years inclusive.
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BMI between 18 to 44.9 kg/m2 at Screening
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Documented history of COPD with a post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator FEV1 ≥ 30% and < 80% predicted at Screening
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Documented stable inhaled treatment regimen of dual therapy or triple therapy for ≥ 3 months prior to Screening.
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Clinically stable and free from an Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the opinion of the Investigator for at least 35 days prior to Day 1
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Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of :
- Non-childbearing potential confirmed at screening
- If considered of childbearing potential, must agree to use with their partner an approved method of highly effective contraception.
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Male participants and their female partners of childbearing potential must be willing to use highly effective contraception measures and must refrain from donating sperm or fathering a child from first day of dosing until 3 months after last IMP dose.
Main Exclusion Criteria:
Parts 1,2 and 3:
- History or presence of gastrointestinal, hepatic, renal, pancreatic disease or acute disease in these organs.
- History of chronic haematologic disease.
- Diagnosis or history of immunodeficiency or increased susceptibility to severe infection, or a clinically significant infection
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- Positive or indeterminate QuantiFERON® Tuberculosis (TB) test at screening.
- Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results
- Any positive result on Screening for serum Hepatitis B surface antigen (HBsAg), hepatitis C antibody and Human immunodeficiency virus (HIV).
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting Electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG.
- Known or suspected history of alcohol and drug abuse in the last year.
- Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the previous 3 months.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD6793.
- Excessive intake of caffeine containing drinks or food
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life
- Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
- Parts 2 and 3 only: Participants who have previously received AZD6793.
Part 4:
- Concurrent enrolment in another clinical study involving an investigational treatment
- Participants unable to perform reproducible spirometry according to American Thoracic Society/ European Respiratory Society [ATS/ERS] criteria at Screening
- Any active medical condition or other reason (at Screening, Day -1, and pre-dose) that would interfere with evaluation of the investigational product or interpretation of participant safety or study results, any other clinically relevant abnormal findings on physical examination or laboratory testing at Screening
- Positive or indeterminate QuantiFERON® TB test at Screening. Indeterminate results may be repeated during Screening.
- Major surgery within 8 weeks prior to Screening
- Donation of blood or blood products in excess of 500 mL within 3 months prior to Screening
- History or current diagnosis of cancer, history of an underlying condition that predisposes the participant to infections, known history of severe reaction to any medication, history of allogeneic bone marrow transplant and history of viral, bacterial or fungal infections within 4 weeks prior to randomisation
- Receiving any immunotherapy or immunosuppressive therapy other than corticosteroids within 6 months of randomisation
- Participants taking metformin during Screening or at any time during the study
- Any participant with active hepatitis or Human immunodeficiency virus (HIV)
- History or presence of vitiligo or significant (in the opinion of the Investigator) skin depigmentation for any cause including drugs
- History of clinically significant chronic/active haematology disease
Trial design
Primary purpose
Allocation
Interventional model
Masking
93 participants in 13 patient groups
Trial contacts and locations
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Central trial contact
AstraZeneca Clinical Study Information Center
Data sourced from clinicaltrials.gov
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