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The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of AZD8965 via single and multiple ascending doses in healthy participants (including Japanese and Chinese participants), and to assess the effect of food on the safety, tolerability, and PK of orally administered AZD8965.
This is a first in human single and multiple ascending dose study. The study consists of 4 parts: Part 1 (single ascending dose [SAD]), Part 2 (multiple ascending dose [MAD]), Part 3A (Japanese and Chinese SAD), Part 3B (Japanese and Chinese combined SAD and MAD), and Part 4 (Food Effect).
Each study part includes a 28-day screening period and a residential period during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until at least 48-72 hours after the study intervention administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: SAD Cohort 1 - AZD8965 (Dose 1) | Experimental | Participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1. |
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| Part 1: SAD Cohort 2 - AZD8965 (Dose 2) | Experimental | Participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1. |
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| Part 1: SAD Cohort 3 - AZD8965 (Dose 3) | Experimental | Participants will receive a single dose of AZD8965 (Dose 3) or matching placebo to AZD8965 on Day 1. |
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| Part 1: SAD Cohort 4 - AZD8965 (Dose 4) | Experimental | Participants will receive a single dose of AZD8965 (Dose 4) or matching placebo to AZD8965 on Day 1. |
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| Part 1: SAD Cohort 5 - AZD8965 (Dose 5) | Experimental | Participants will receive a single dose of AZD8965 (Dose 5) or matching placebo to AZD8965 on Day 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD8965 | Drug | AZD8965 will be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 3A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) | To assess the safety and tolerability of AZD8965 following oral administration of single ascending doses to healthy participants. | SAEs: From Screening (Day -28) to 5 weeks; AEs: From Day 1 to 5 weeks |
| Parts 2 and 3B: Number of participants with AEs and SAEs | To assess the safety and tolerability of AZD8965 following oral administration of multiple ascending doses to healthy participants. | SAEs: From Screening (Day -28) to 8 weeks; AEs: From Day 1 to 8 weeks. |
| Part 4: Maximum observed drug concentration (Cmax) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Area under concentration-time curve from time 0 to infinity (AUCinf) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Time to reach maximum observed concentration (tmax) |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1, 2, 3A and 3B: Maximum observed drug concentration (Cmax) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
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Inclusion Criteria:
Healthy male and female participants (including Japanese and Chinese participants) with suitable veins for cannulation or repeated venipuncture.
All females of childbearing potential must have a negative pregnancy test at the Screening Visit (serum) and on admission (urine) to the Clinical Unit.
All females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception with low user dependency and their non-sterilized male partners must use a condom, to avoid pregnancy from the time of first administration of study intervention until 20 days after the last dose of study intervention. Females must not use hormonal contraceptives or hormone replacement therapy during the study.
Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:
Sexually active fertile male participants with partners of childbearing potential must adhere to the specified contraception methods from the time of first administration of study intervention administration until 20 days after the last dose of study intervention.
Have a body mass index (BMI) between 18 and 30 kilogram (kg)/square meter (m2) inclusive and weigh at least 45 kg.
Part 3A and Part 3B (Japanese Participants)
Healthy Japanese participants are eligible based on meeting all of the following:
Healthy Chinese participants. Participants of Chinese ancestry are eligible based on meeting all of the following:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Glendale | California | 91206 | United States |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| Part 2: MAD Cohort 1 - AZD8965 (Dose 1) | Experimental | Participants will receive multiple doses of AZD8965 (Dose 1) or matching placebo to AZD8965 from Day 1 to Day 8. |
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| Part 2: MAD Cohort 2 - AZD8965 (Dose 2) | Experimental | Participants will receive multiple doses of AZD8965 (Dose 2) or matching placebo to AZD8965 from Day 1 to Day 8. |
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| Part 2: MAD Cohort 3 - AZD8965 (Dose 3) | Experimental | Participants will receive multiple doses of AZD8965 (Dose 3) or matching placebo to AZD8965 from Day 1 to Day 8. |
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| Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1) | Experimental | Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1. |
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| Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2) | Experimental | Japanese participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1. |
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| Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1) | Experimental | Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1. |
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| Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1) | Experimental | Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9. |
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| Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1) | Experimental | Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9. |
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| Part 4: Food Effect Cohort - AZD8965 | Experimental | Participants will receive 2 single dose treatments of AZD8965 [following an overnight fast of at least 10 hours in a fasted state or a fed state (after a high fat meal)]. |
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| Placebo | Other | Placebo will be administered orally. |
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To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. |
| From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)] | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Terminal elimination half-life (t½λz) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Mean Residence Time (MRTinf) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Apparent total body clearance (CL/F) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Apparent volume of distribution based on the terminal (Vz/F) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Accumulation ratio for AUC (Rac AUC) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Accumulation ratio for Cmax (Rac Cmax) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 5 |
| Part 4: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 5 |
| Part 4: Relative bioavailability calculated as test AUC/reference AUC (Frel AUC) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Relative bioavailability calculated as test Cmax/reference Cmax (Frel Cmax) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 7 (72-hour post dose) |
| Part 4: Renal clearance (CLR) | To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 5 |
| Parts 1, 2, 3A and 3B: Area under concentration-time curve from time 0 to infinity (AUCinf) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Time to reach maximum observed concentration (tmax) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)] | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Terminal elimination half-life (t½λz) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Mean Residence Time (MRTinf) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Apparent total body clearance (CL/F) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Apparent volume of distribution based on the terminal (Vz/F) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 1, 2, 3A and 3B: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9 |
| Parts 1, 2, 3A and 3B: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9 |
| Parts 1, 2, 3A and 3B: Renal clearance (CLR) | To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants. | Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9 |
| Parts 2 and 3B: Area under concentration-time curve in the dosing interval (AUCtau) | To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 2 and 3B: Accumulation ratio for AUC (Rac AUC) | To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 2 and 3B: Accumulation ratio for Cmax (Rac Cmax) | To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Parts 2 and 3B: Temporal Change Parameter (TCP) | To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants. | From Day 1 (pre-dose) to Day 10 (48-hour post dose) |
| Part 4: Number of participants with AEs and SAEs | To assess the safety and tolerability of AZD8965 under fasted and fed (after intake of a high fat meal) conditions in healthy participants. | SAEs: From Screening (Day -28) to 6 weeks; AEs: From Day 1 to 6 weeks |
| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| D008171 | Lung Diseases |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D012140 | Respiratory Tract Diseases |
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