Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ALXN2050
ACH-0145228: Immediate Release · 9 trials · 2 indications
see Time Frame - defined
see Time Frame - defined
see Time Frame - defined
see Time Frame - defined
see Time Frame - defined
see Time Frame - defined
see Time Frame - defined
Mass balance will be assessed by evaluating total radioactivity recovery and the percent of the radioactive dose excreted in the urine and feces. Mass balance will be calculated as a sum of the percent of the total radioactivity recovered in urine and feces plus any radioactivity dose lost due to emesis (if any occurred) relative to the administered radioactivity dose.
ALXN2050 metabolic profiling in plasma, urine, and feces will be performed in samples containing sufficient amounts of radioactivity. The percent of dose represented by each of the metabolites will be calculated using the radioactivity concentration equivalent data combined with the metabolic profiling data. The percentage of each identified metabolite to total radioactivity in plasma will be estimated based on plasma metabolic profiling data.
Twelve-lead electrocardiograms (ECGs) will be extracted from continuous (Holter) recordings.
Relative bioavailability will be measured by the ratio of the area under the concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf).
| Arm | Type | Description |
|---|---|---|
| Part 1 - Cyclosporine | EXPERIMENTAL | Participants will receive ALXN2050 and cyclosporine in a fixed sequence over 3 periods. Period 1: Participants will receive multiple doses of ALXN2050. Period 2: Participants will receive multiple doses of cyclosporine. Period 3: Participants will receive multiple doses of ALXN2050 co-administered with multiple doses of cyclosporine. There will be a washout period between the last dose of ALXN2050 in Period 1 and the first dose of cyclosporine in Period 2 and between the last dose of cyclosporine in Period 2 and the first dosing in Period 3. |
| Part 2 - Tacrolimus | EXPERIMENTAL | Participants will receive tacrolimus and ALXN2050 in a fixed sequence over 2 periods. Period 1: Participants will receive a single dose of tacrolimus. Period 2: Participants will receive multiple doses of ALXN2050 alone and co-administered with a single dose of tacrolimus. There will be a washout period between the dose of tacrolimus in Period 1 and the first dose of ALXN2050 in Period 2. |
| Part 3 - MMF | EXPERIMENTAL | Participants will receive MMF and ALXN2050 in a fixed sequence over 2 periods. Period 1: Participants will receive a single dose of MMF. Period 2: Participants will receive multiple doses of ALXN2050 alone and co-administered with a single dose of MMF. There will be a washout period between the dose of MMF in Period 1 and the first dose of ALXN2050 in Period 2. |
| Cohort 1: ALXN2050 (Dose 1) | EXPERIMENTAL | Participants will receive ALXN2050 (Dose 1) as follows under fasting conditions: 120-milligrams (mg) single dose, 3-day washout, then 120-mg twice daily (BID) dosing. |
| Cohort 1: Placebo (Dose 1) | EXPERIMENTAL | Participants will receive placebo (Dose 1) as follows under fasting conditions: 120-mg placebo single dose, 3-day washout, then 120-mg placebo BID dosing. |
| Cohort 2: ALXN2050 (Dose 2) | EXPERIMENTAL | Participants will receive ALXN2050 (Dose 2) as follows under fasting conditions: 180-mg single dose, 3-day washout, then 180-mg BID dosing. |
| Cohort 2: Placebo (Dose 2) | EXPERIMENTAL | Participants will receive placebo (Dose 2) as follows under fasting conditions: 180-mg placebo single dose, 3-day washout, then 180-mg placebo BID dosing. |
| Cohort 1: Severe Impaired Renal Function | EXPERIMENTAL | Participants will receive ALXN2050. |
| Cohort 2: Moderate Impaired Renal Function | EXPERIMENTAL | Participants will receive ALXN2050. |
| Cohort 3: Mild Impaired Renal Function | EXPERIMENTAL | Participants will receive ALXN2050. |
| Cohort 4: Healthy Control | EXPERIMENTAL | Participants will receive ALXN2050. |
| Part 1: ALXN2050 plus Fluconazole | EXPERIMENTAL | Period 1: Participants will receive a single dose of ALXN2050 alone and in the presence of multiple doses of fluconazole. Period 2: Participants will receive multiple doses of ALXN2050 alone and in the presence of multiple doses of fluconazole. Scheduled pharmacokinetics (PK) blood samples for both ALXN2050 and fluconazole will be collected, with a washout period of at least 14 days between the last dose of fluconazole in Period 1 and the first dose of ALXN2050 in Period 2. |
| Part 2: ALXN2050 plus Rifampin | EXPERIMENTAL | Participants will receive a single dose of ALXN2050 alone and in the presence of both single and multiple doses of rifampin. Scheduled PK blood samples for both ALXN2050 and rifampin will be collected. |
| [14C]-ALXN2050 | EXPERIMENTAL | Participants will receive \[14C\]-ALXN2050. |
| Treatment Arm (ABC) | EXPERIMENTAL | Treatment Sequence ABC - Participants will receive all 3 doses of ALXN2050 in a multiple-ascending fashion over 3 periods: Treatment A (Period 1): ALXN2050 Dose 120 milligrams (mg) and moxifloxacin-matching placebo. Treatment B (Period 2): ALXN2050 Dose 240 mg and moxifloxacin-matching placebo. Treatment C (Period 3): ALXN2050 Dose 360 mg and moxifloxacin-matching placebo. |
| Control Arm (DEF) | PLACEBO_COMPARATOR | Treatment Sequence DEF - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment D (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment E (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin. Treatment F (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. |
| Control Arm (GHI) | PLACEBO_COMPARATOR | Treatment Sequence GHI - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment G (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin. Treatment H (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment I (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin. |
| Sequence 1 | EXPERIMENTAL | Participants will receive ACH-0145228 once each Period as a single dose under fasted or fed conditions as follows: Period 1: ACH-0145228 as an immediate-release tablet under fasted conditions (test-fasted). Period 2: ACH-0145228 as an immediate-release tablet under fed conditions (test-fed). Period 3: ACH-0145228 as power-in-capsule under fasted conditions (reference). There will be a washout period of at least 5 days between each ACH-0145228 dosing. |
| Sequence 2 | EXPERIMENTAL | Participants will receive ACH-0145228 once each Period as a single dose under fasted or fed conditions as follows: Period 1: ACH-0145228 as an immediate-release tablet under fed conditions (test-fed). Period 2: ACH-0145228 as power-in-capsule under fasted conditions (reference). Period 3: ACH-0145228 as an immediate-release tablet under fasted conditions (test-fasted). There will be a washout period of at least 5 days between each ACH-0145228 dosing. |
| Sequence 3 | EXPERIMENTAL | Participants will receive ACH-0145228 once each Period as a single dose under fasted or fed conditions as follows: Period 1: ACH-0145228 as power-in-capsule under fasted conditions (reference). Period 2: ACH-0145228 as an immediate-release tablet under fasted conditions (test-fasted). Period 3: ACH-0145228 as an immediate-release tablet under fed conditions (test-fed). There will be a washout period of at least 5 days between each ACH-0145228 dosing. |
| Cohort 1: 40 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive ALXN2050 or placebo twice daily (BID) on Day 1 through Day 14 in a fasted state. |
| Cohort 2: 80 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. |
| Cohort 3: 120 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. |
| Cohort 4: 200 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive ALXN2050 or placebo BID on Day 1 through Day 14 in a fasted state. |
| Cohort 5: 120 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fed state. |
| Cohort 6: 240 mg ALXN2050/Placebo | EXPERIMENTAL | Participants randomized to receive a single dose of ALXN2050 or placebo on Day 1 in a fasted state. |
| Name | Type | Description |
|---|---|---|
| ALXN2050 | DRUG | Oral tablet. |
| Cyclosporine | DRUG | Oral capsule. |
| Tacrolimus | DRUG | Oral capsule. |
| MMF | DRUG | Oral tablet. |
| Placebo | DRUG | Oral tablet. |
| Fluconazole | DRUG | Oral tablet. |
| Rifampin | DRUG | Oral capsule. |
| [14C]-ALXN2050 | DRUG | A single dose of 200 milligrams (\~85 microcuries) \[14C\]-ALXN2050 will be administered orally. |
| ALXN2050-matching Placebo | DRUG | ALXN2050-matching placebo will be administered orally twice daily as placebo powder-in-capsule. |
| Moxifloxacin | DRUG | Moxifloxacin will be administered as a single oral dose. |
| Moxifloxacin-matching Placebo | DRUG | Moxifloxacin-matching placebo will be administered as a single oral dose. |
| ACH-0145228: Immediate Release | DRUG | ACH-0145228 (240 milligrams) will be administered orally on Day 1. |
| ACH-0145228: Powder-in-capsule | DRUG | ACH-0145228 (240 milligrams) will be administered orally on Day 1. |
Inclusion Criteria: * Medically healthy with no clinically significant or relevant abnormalities as determined by medical history, physical or neurological examination, vital signs, 12-lead electrocardiogram, screening clinical laboratory profiles (hematology, biochemistry, coagulation, and urinaly...
ACH-0145228: Immediate Release is an investigational small molecule developed by AstraZeneca PLC. It is formulated as an immediate release tablet and was studied in healthy adult participants. The specific therapeutic indication has not been disclosed. It remains in clinical development and is not approved for any use.
ACH-0145228: Immediate Release is being developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. AstraZeneca is the sponsor of the clinical program for this investigational small molecule.
ACH-0145228: Immediate Release is in Phase 1 clinical development. One Phase 1 trial has been completed, and no active trials are currently listed. The drug is investigational and has not been approved by the FDA or any other regulatory agency.
ACH-0145228: Immediate Release has been evaluated in one completed Phase 1 trial, NCT04551586. The study compared the immediate release tablet formulation to a powder-in-capsule formulation in 28 healthy adult participants in the United States. It was randomized and controlled but not double-blind.
The therapeutic indication for ACH-0145228: Immediate Release has not been disclosed. The completed Phase 1 trial enrolled healthy adult volunteers rather than patients with a specific disease, so no clinical indication has been publicly identified for this investigational small molecule.