Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD2389 · 8 trials · 5 indications
To evaluate the effects of AZD2389 versus placebo on improvement in ELF score. Lowered ELF scores would suggest better outcome. Note: ELF is not bounded, i.e. there are no minimum and maximum values
To assess the safety and tolerability of AZD2389 in participants with SLD and advanced fibrosis
Assess blood pressure level (with systolic and diastolic pressure) in mmHg
12-lead safety ECG (PR interval, QRS complex, ST interval, T wave)
Urinalysis - Paper chromatography
Pulse rate measured in beats per minute (BPM)
Sp02 oxygen saturations measured by percentage
Body temperature measured in degrees Celsius
Respiratory rate measured in respirations per minute
Hematology - Platelets (x10\^9/L)
The number of participants with notable trends in laboratory assessments (haematology, coagulation, clinical chemistry, fibrinolysis, and urinalysis) is presented. Notable trends were assessed based on evaluation of mean values over time, individual participant values, and clinically important abnormalities, including values outside predefined criteria.
The number of participants with clinically relevant trends in vital signs (blood pressure, pulse rate, oxygen saturation, body temperature, and respiration rate), and12-lead ECGs is presented. Clinically relevant trends were assessed based on trends or group changes over time, changes in individual participants over time, and individual clinically important abnormalities.
To examine target FAP occupancy in the liver by AZD2389 as measured with \[68Ga\]Ga-FAPI-46 PET.
To assess the effect of quinidine on the PK of AZD2389.
To assess the effect of quinidine on the PK of AZD2389.
To assess the effect of quinidine on the PK of AZD2389.
To assess the PK parameter RCmax for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter RAUCinf for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter RAUClast for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter ratio of AUC0-24 for caffeine in combination with AZD2389 compared to caffeine alone.
To assess the effect of itraconazole on the Cmax of AZD2389.
To assess the effect of itraconazole on the AUCinf of AZD2389.
To assess the effect of itraconazole on the AUClast of AZD2389.
maximum observed plasma concentration
area under the concentration-time curve from zero to infinity
area under the concentration-time curve from zero to the last measurable concentration
To assess the safety and tolerability of AZD2389 following oral administration of single ascending doses in healthy participants, including Japanese and Chinese participants.
To assess the safety and tolerability of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Doses of AZD2389 to be administered orally. |
| Arm B | PLACEBO_COMPARATOR | Doses of placebo to be administered orally. |
| Cohort A | OTHER | Participants with presumed MASH/NASH with fibrosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo. |
| Cohort B | OTHER | Participants with SLD with advanced fibrosis including compensated cirrhosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo. |
| Part A | OTHER | In Part A, eligible participants (screening Visit 1) will return to the trial site for pre-assessments, confirmation of eligibility criteria, blood sampling for FAP concentration analysis (at the trial site), and the first PET examination (screening Visit 2). The participants will perform the PET examination at the PET Centre using the radioligand \[68Ga\]Ga-FAPI-46. Depending on the results of the initial PET examination, participants of Part A may be invited to continue the trial in Part B. In such a case they will participate in a total of 3 PET examinations, not exceeding predefined radiation exposure limits. If they do not participate further, they will complete the trial with a follow-up visit (Visit 3, telephone call) 7 days (±2 days) after the PET examination. |
| Part B1 | EXPERIMENTAL | In Part B1, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part B2 | EXPERIMENTAL | In Part B2, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part B3 | EXPERIMENTAL | In Part B3, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part C | EXPERIMENTAL | In Part C (optional), participants attend the trial site during Visit 1 (screening, Day-35 to Day-14) to undergo an eligibility check. At Visit 2, the first PET examination with radioligand will be performed at least 5 days before IMP administration. At Visit 3 (Day 1), participants receive a single dose AZD2389, then undergo a second PET examination using the radioligand on Day 2, along with blood sampling for PK analysis and FAP activity. At Visit 4 (Day 8 ±2 days), participants will be admitted to the trial site for a second single dose, then undergo a third PET examination using the radioligand on Day 9, along with blood sampling. At Visit 5 (7 days ±2 days after the PET examination on Visit 4) and Visit 6 (30 days \[+7 days\]) after the drug administration on Visit 4), follow-up visits at the trial site take place for safety monitoring and follow-up of any AEs. |
| Sequence AB | EXPERIMENTAL | Participants will receive a single dose of Treatment A (AZD2389) in Period 1 and a single dose of Treatment B (AZD2389 + quinidine) in Period 2. |
| Sequence BA | EXPERIMENTAL | Participants will receive a single dose of Treatment B (AZD2389 + quinidine) in Period 1 and a single dose of Treatment A (AZD2389) in Period 2. |
| Treatment Arm | EXPERIMENTAL | In Period 1, participants will receive midazolam and caffeine in combination on Day 1. Participants will receive bupropion on Day 2. In Period 2, participants will receive AZD2389 for 9 days from Day 5 to Day 13. In Period 3, participants will first receive AZD2389 with midazolam and caffeine in combination on Day 14. On Day 15, participants will first receive AZD2389 with bupropion. On Days 16 and 17, participants will receive AZD2389. |
| AZD2389 and Itraconazole | EXPERIMENTAL | AZD2389 is dosed on days 1 and 6. Itraconazole is dosed on days 3,4,5,6,7, with the dose on day 6 coming after AZD2389. |
| Cohort 1 | EXPERIMENTAL | Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched) |
| Cohort 2 | EXPERIMENTAL | Participants with mild hepatic impairment (CP A classification) |
| Cohort 3 | EXPERIMENTAL | Participants with moderate hepatic impairment (CP B classification) |
| Cohort 4 | EXPERIMENTAL | Participants with severe hepatic impairment (CP C classification) |
| Cohort 1: Part A1 - AZD2389 dose 1/placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 2: Part A1 - AZD2389 dose 2/placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 3: Part A1 - AZD2389 dose 3 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 4: Part A1 - AZD2389 dose 4 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 5: Part A1 - AZD2389 dose 5 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 6: Part A1 - AZD2389 dose 6 oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389. |
| Cohort 7: Part A2 - AZD2389 dose 7 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 8: Part A2 - AZD2389 dose 8 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 9: Part A2 - AZD2389 dose 9 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 10: Part A3 - AZD2389 dose 10 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive a single dose of AZD2389 and 2 will receive placebo. |
| Cohort 11: Part B1 - AZD2389 dose 11 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive multiple doses of AZD2389 and 2 will receive placebo. |
| Cohort 12: Part B1 - AZD2389 dose 12 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive multiple doses of AZD2389 and 2 will receive placebo. |
| Cohort 13: Part B1 - AZD2389 dose 13 /placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive multiple doses of AZD2389 and 2 will receive placebo. |
| Cohort 14: Part B2- AZD2389 dose 14/placebo oral administration | EXPERIMENTAL | A total of 6 study participants will receive multiple doses of AZD2389 and 2 will receive placebo. |
| Name | Type | Description |
|---|---|---|
| AZD2389 | DRUG | potent, selective, first-in-class, small molecule oral inhibitor of FAP and is being developed for the treatment of CLDs with advanced hepatic fibrosis including cirrhosis. |
| Placebo | OTHER | Oral administration |
| PET scan and radioligand | DIAGNOSTIC_TEST | PET scan and radioligand |
| Quinidine | DRUG | Quinidine will be administered orally. |
| Midazolam | DRUG | Single oral dose on: * Day 1 (co-administered with caffeine) * Day 14 (co-administered with caffeine and AZD2389) |
| Caffeine | DRUG | Single oral dose on: * Day 1 (co-administered with midazolam) * Day 14 (co-administered with midazolam and AZD2389) |
| Bupropion | DRUG | Single oral dose on: * Day 2 (alone) * Day 15 (co-administered with AZD2389) |
| Itraconazole | DRUG | Itraconazole is administered orally |
Key Inclusion Criteria: * Males/females aged 18 or over * A diagnosis of SLD with advanced fibrosis * No significant change in weight over the last 6 months * Contraceptive us by participants or participants partners * Capable of giving informed consent * Judged by the investigator to be suitable f...
AZD2389 is an investigational small molecule being developed by AstraZeneca for gastrointestinal conditions, including liver fibrosis, hepatic impairment, and advanced chronic liver disease. It is currently in Phase 1 clinical development, with studies conducted in healthy participants and those with liver-related conditions.
AZD2389 is being developed by AstraZeneca PLC, a multinational pharmaceutical company traded on the NASDAQ under the ticker symbol AZN. The drug is currently in Phase 1 clinical trials, with studies focused on healthy participants and individuals with hepatic impairment or advanced chronic liver disease.
AZD2389 is in Phase 1 clinical development. It has completed several Phase 1 studies, including trials in healthy participants and those with hepatic impairment. The drug is investigational and has not been approved by regulatory authorities, as it is still undergoing early-stage clinical evaluation.
AZD2389 has been studied in several Phase 1 trials, including NCT06138795, a single and multiple ascending dose study in healthy participants; NCT06812780, a hepatic impairment study; NCT06846528, a drug interaction study with itraconazole; and NCT06973005, a study examining interactions with midazolam, caffeine, and bupropion.
No alternative names for AZD2389 have been reported. It is identified solely by its development code AZD2389, and no other brand names or aliases are currently associated with this investigational compound.