Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD5004 · 11 trials · 6 indications
To determine whether AZD5004 is superior to placebo for weight loss
To determine whether AZD5004 is superior to placebo on achieving weight loss ≥ 5% from baseline
To evaluate the effect of AZD5004 versus placebo on glycemic control
To assess the effect of AZD5004 on the PK (AUCinf) of mitiglinide and pioglitazone in healthy participants
To assess the effect of AZD5004 on the PK (AUClast) of mitiglinide and pioglitazone in healthy participants
To assess the effect of AZD5004 on the PK (Cmax) of mitiglinide and pioglitazone in healthy participants
To evaluate the PK (AUCinf) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
To evaluate the PK (AUClast) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
To evaluate the PK (Cmax) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
To assess the effect of multiple doses of itraconazole on the AUCinf of a single dose of AZD5004 in healthy male and female participants.
To assess the effect of multiple doses of itraconazole on the AUClast of a single dose of AZD5004 in healthy male and female participants
To assess the effect of multiple doses of itraconazole on the Cmax of a single dose of AZD5004 in healthy male and female participants
To assess the effect of multiple doses of itraconazole on the t1/2λz of a single dose of AZD5004 in healthy male and female participants
To assess the effect of multiple doses of itraconazole on the tmax of a single dose of AZD5004 in healthy male and female participants
To assess the effect of multiple doses of itraconazole on the CL/F of a single dose of AZD5004 in healthy male and female participants
To assess the effect of multiple doses of itraconazole on the Vz of a single dose of AZD5004 in healthy male and female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the AUCinf of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the AUClast of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the Cmax of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the t1/2λz of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the tmax of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the CL/F of single doses of combined oral EE/LNG in healthy female participants
To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the Vz of single doses of combined oral EE/LNG in healthy female participants
To assess the relative bioavailability of AZD5004 in 3 different solid oral formulations (F1, F3, F4)
To assess the relative bioavailability of AZD5004 in 3 different solid oral formulations (F1, F3, F4)
To assess the relative bioavailability of AZD5004 in 3 different solid oral formulations (F1, F3, F4)
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.
Part A: To assess the Ratio of Rosuvastatin (Rosuvastatin + AZD5004) to Rosuvastatin (alone) and Ratio of AZD5004 (AZD5004 + erythromycin) to AZD5004 (alone) based on AUCinf. Part B: To assess the Ratio of Atorvastatin or Simvastatin (Atorvastatin/Simvastatin + AZD5004) to Atorvastatin or Simvastatin (alone) based on AUCinf. Part C: To assess the Ratio of Repaglinide (Repaglinide + AZD5004) to Repaglinide (alone) based on AUCinf.
Part A: To assess the Ratio of Rosuvastatin (Rosuvastatin + AZD5004) to Rosuvastatin (alone) and Ratio of AZD5004 (AZD5004 + erythromycin) to AZD5004 (alone) based on AUClast. Part B: To assess the Ratio of Atorvastatin or Simvastatin (Atorvastatin/Simvastatin + AZD5004) to Atorvastatin or Simvastatin (alone) based on AUClast. Part C: To assess the Ratio of Repaglinide (Repaglinide + AZD5004) to Repaglinide (alone) based on AUClast.
Part A: To assess the Ratio of Rosuvastatin (Rosuvastatin + AZD5004) to Rosuvastatin (alone) and Ratio of AZD5004 (AZD5004 + erythromycin) to AZD5004 (alone) based on Cmax. Part B: To assess the Ratio of Atorvastatin or Simvastatin (Atorvastatin/Simvastatin + AZD5004) to Atorvastatin or Simvastatin (alone) based on Cmax. Part C: To assess the Ratio of Repaglinide (Repaglinide + AZD5004) to Repaglinide (alone) based on Cmax.
Area under plasma concentration-time curve from zero to infinity
Area under plasma concentration-time curve from time zero to the last measurable concentration
Maximum observed plasma concentration
To assess the safety and tolerability of AZD5004 following single oral doses in healthy participants.
To assess the safety and tolerability of AZD5004 following multiple oral ascending doses in participants with T2DM.
To assess the safety and tolerability of AZD5004 following oral multiple ascending doses in healthy participants.
To evaluate the Cmax of 2 treatments of AZD5004 in healthy participants.
To evaluate the AUClast of 2 treatments of AZD5004 in healthy participants.
To evaluate the AUCinf of 2 treatments of AZD5004 in healthy participants.
To evaluate the tmax of 2 treatments of AZD5004 in healthy participants.
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | Active IMP |
| Arm 2 | EXPERIMENTAL | Active IMP |
| Arm 3 | EXPERIMENTAL | Active IMP |
| Arm 4 | EXPERIMENTAL | Active IMP |
| Arm 5 | EXPERIMENTAL | Active IMP |
| Arm 6 | PLACEBO_COMPARATOR | Matching placebo for each of the 5 active arms |
| Arm 7 | ACTIVE_COMPARATOR | Participants will receive once daily dose of Semaglutide as active comparator |
| Arm 8 | PLACEBO_COMPARATOR | Participants will receive matching placebo for each AZD5004 arm |
| Part A: Mitiglinide + AZD5004 | EXPERIMENTAL | In Period 1, participants receive a single dose of mitiglinide on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 3-9, then single doses of AZD5004 Dose B once daily from Days 10-16. In Period 2, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose B on Day 17, followed by a single dose of AZD5004 Dose B on Day 18, then single doses of AZD5004 Dose C once daily from Days 19-25, followed by single doses of AZD5004 Dose D once daily from Days 26-32. In Period 3, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose D on Day 33, followed by a single dose of AZD5004 Dose D on Day 34, then single doses of AZD5004 Dose E once daily from Days 35-41. In Period 4, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose E on Day 42, followed by a single dose of AZD5004 Dose E on Day 43. |
| Part B: Pioglitazone + AZD5004 | EXPERIMENTAL | In Period 1, participants receive a single dose of pioglitazone on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 8-14, then single doses of AZD5004 Dose B once daily from Days 15-21. In Period 2, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose B on Day 22, followed by single doses of AZD5004 Dose B once daily from Days 23-28, then single doses of AZD5004 Dose C once daily from Days 29-35, followed by single doses of AZD5004 Dose D once daily from Days 36-42. In Period 3, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose D on Day 43, followed by single doses of AZD5004 Dose D once daily from Days 44-49, then single doses of AZD5004 Dose E once daily from Days 50-56. In Period 4, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose E on Day 57, followed by single doses of AZD5004 Dose E once daily from Days 58-63. |
| Cohort A: Treatment Sequence ABC | EXPERIMENTAL | Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen B (formulation 5, fasted state), followed by Regimen C (formulation 5, fed state) of AZD5004. |
| Cohort A: Treatment Sequence ACB | EXPERIMENTAL | Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen C (formulation 5, fed state), followed by Regimen B (formulation 5, fasted state) of AZD5004. |
| Cohort B: Treatment Sequence ADE | EXPERIMENTAL | Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen D (formulation 6, fasted state), followed by Regimen E (formulation 6, fed state). |
| Cohort B: Treatment Sequence AED | EXPERIMENTAL | Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen E (formulation 6, fed state), followed by Regimen D (formulation 6, fasted state). |
| Part A: AZD5004 + Itraconazole | EXPERIMENTAL | Participants will receive oral dose of AZD5004 on Period 1, followed by Itraconazole capsule orally in Period 2, and then will receive oral dose of AZD5004 combination with Itraconazole capsule in Period 3. |
| Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004 | EXPERIMENTAL | Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally. |
| Treatment Sequence A | EXPERIMENTAL | Participants will receive single dose of AZD5004 on Day 1 in F1 (fasted) (Treatment period 1), on Day 8 in F4 (fasted) (Treatment period 2), on Day 15 in F4(fed) (Treatment Period 3) followed by on Day 22 in F3 (fasted) (Treatment Period 4) respectively. |
| Treatment Sequence B | EXPERIMENTAL | Partcipants will receive single dose of AZD5004 on Day 1 in F4 (fasted) (Treatment Period 1), on Day 8 in F4 (fed) (Treatment Period 2), on Day 15 in F3 (fasted) (Treatment Period 3) followed by on Day 22 in F1 (fasted) (Treatment Period 4) respectively. |
| Treatment Sequence C | EXPERIMENTAL | Participants will receive single dose of AZD5004 on Day 1 in F4 (fed) (Treatment Period 1), on Day 8 in F3 (fasted) (Treatment Period 2, on Day 15 in F1 (fasted) (Treatment Period 3 followed by on Day 22 in F4 (fasted) (Treatment Period 4) respectively. |
| Treatment Sequence D | EXPERIMENTAL | Participants will receive single dose of AZD5004 on Day 1 in F3 (fasted) (Treatment Period 1), Day 8 in F1 (fasted) (Treatment Period 2), on Day 15 in F4 (fasted) (Treatment Period 3) followed by Day 22 in F4 (fed) (Treatment Period 4) respectively. |
| Part A | EXPERIMENTAL | Participants will receive 10 mg rosuvastatin in Period 1. Participants will receive 10 mg rosuvastatin and AZD5004 in Period 2. Later, participants will receive different doses of AZD5004 followed by 10 mg single dose of rosuvastatin in Period 3, Period 4, Period 5, and Period 6. In Period 7, participants will receive AZD5004 alone and later, 500 mg erythromycin twice a day. Participants will receive 500 mg erythromycin co-administered with AZD5004 during Period 8. |
| Part B | EXPERIMENTAL | Participants will receive 20 mg simvastatin during Period 1. In Period 2, participants will receive 40mg atorvastatin. In Period 3, participants will receive 40 mg atorvastatin and then, AZD5004 once daily . During Period 4, participants will receive 40 mg atorvastatin with single dose of AZD5004 and later, two different doses of AZD5004 alone will be administered once a day. In Period 5, participants will receive 20 mg simvastatin with single dose of AZD5004, later, AZD5004 alone will be administered once a day. During Period 6, participants will receive 40 mg atorvastatin with single dose of AZD5004 initially, and later AZD5004 will be administered once daily. In Period 7, participants will receive AZD5004 followed by 40 mg single dose of atorvastatin. |
| Part C | EXPERIMENTAL | Participants will receive 0.5 mg repaglinide initially during Period 1, later AZD5004 once daily will be administered . Participants will then receive 0.5 mg repaglinide with single dose of AZD5004 in Period 2, later two different doses of AZD5004 once daily will be administered. In Period 3, participants will receive 0.5 mg repaglinide with single dose of AZD5004 initially, and later AZD5004 once daily will be administered. In Period 4, participants will receive 0.5 mg repaglinide with single dose of AZD5004. |
| Group 1 | EXPERIMENTAL | A single oral dose of AZD5004 under fasted conditions. |
| Group 2 | EXPERIMENTAL | A single oral dose of AZD5004 under fasted conditions. |
| Group 3 | EXPERIMENTAL | A single oral dose of AZD5004 under fasted conditions. |
| Group 4 | EXPERIMENTAL | A single oral dose of AZD5004 under fasted conditions. |
| Group 3 (Optional) | EXPERIMENTAL | Participants with moderate renal impairment will receive a single oral dose of AZD5004 under fasted conditions. |
| Part A-AZD5004 | EXPERIMENTAL | Participants will receive AZD5004 orally. |
| Part A-Placebo | PLACEBO_COMPARATOR | Participants will receive matching Placebo orally. |
| Part B-AZD5004 | EXPERIMENTAL | Participants will receive AZD5004 orally. |
| Part B-Placebo | PLACEBO_COMPARATOR | Participants will receive matching Placebo orally. |
| Part A: Multiple Ascending dose (MAD) (AZD5004) | EXPERIMENTAL | Participants will receive repeated dosing of AZD5004 orally. |
| Part A: Placebo | PLACEBO_COMPARATOR | Participants will receive matching Placebo orally. |
| Part B: Treatment 1 (AZD5004) | EXPERIMENTAL | Participants in Group 1 will receive Treatment 1 of AZD5004 and then Treatment 2 of AZD5004. Participants in Group 2 will receive Treatment 2 of AZD5004 and then Treatment 1 of AZD5004. |
| Part B: Treatment 2 (AZD5004) | EXPERIMENTAL | Participants in Group 1 will receive Treatment 1 of AZD5004 and then Treatment 2 of AZD5004. Participants in Group 2 will receive Treatment 2 of AZD5004 and then Treatment 1 of AZD5004. |
| Name | Type | Description |
|---|---|---|
| AZD5004 | DRUG | AZD5004 film-coated tablet once daily during 36 weeks |
| Placebo | DRUG | Placebo matching AZD5004 film-coated tablet once daily during 36 weeks |
| Placebo (placebo matching AZD5004 film-coated tablet) | DRUG | Placebo film-coated tablet (matching AZD5004) |
| Semaglutide | DRUG | 3-14 mg tablets of Semaglutide |
| Mitiglinide | DRUG | Mitiglinide will be administered orally. |
| Pioglitazone | DRUG | Pioglitazone will be administered orally. |
| Itraconazole | DRUG | Itraconazole is administered orally as a capsule. |
| EE/LNG | DRUG | EE/LNG is administered orally in the form of tablet. |
| Rosuvastatin | DRUG | Participants will receive single oral tablets of rosuvastatin 10mg on Days 1, 7, 14, 21, 28, and 35. |
| Erythromycin | DRUG | Participants will receive oral doses of erythromycin 500 mg, twice a day from Day 49 to Day 54; and a single dose of 500 mg on Day 55. |
| Atorvastatin | DRUG | Participants will receive single oral doses of 40 mg atorvastatin on Days 4, 8, 16, 38, and 42. |
| Simvastatin | DRUG | Participants will receive single oral doses of 20 mg simvastatin on Days 1 and 31. |
| Repaglinide | DRUG | Participants will receive single oral doses of 0.5 mg repaglinide on Days 1, 10, 26, and 34. |
| AZD5004(Part A) | DRUG | Single dose of AZD5004 oral on Day1 |
| Placebo(Part A) | DRUG | Single dose of placebo oral on Day1 |
| AZD5004(Part B) | DRUG | AZD5004 will be administered as an oral tablet once daily. |
| Placebo(Part B) | DRUG | Placebo will be administered as an oral tablet once daily. |
Inclusion Criteria: * Adults ≥ 18 years of age. * BMI of (a) ≥ 30 kg/m2, or (b) ≥ 27 kg/m2 and have a current diagnosis of at least 1 of the following weight-related comorbidities (treated or untreated): (i) Hypertension (ii) Dyslipidemia or hyperlipidemia (iii) CV disease (iv) Obstructive sleep...