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This study will investigate the impact of impaired renal function on the plasma pharmacokinetics of ALXN2050 in order to provide dosing recommendations for future indications in individuals with impaired renal function.
The study will initiate (Part 1) with participants with severe impaired renal function (Cohort 1) and their matched healthy control participants (Cohort 4). Following data review, the study may proceed (Part 2) with participants with moderate (Cohort 2) and mild (Cohort 3) impaired renal function if deemed necessary.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Severe Impaired Renal Function | Experimental | Participants will receive ALXN2050. |
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| Cohort 2: Moderate Impaired Renal Function | Experimental | Participants will receive ALXN2050. |
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| Cohort 3: Mild Impaired Renal Function | Experimental | Participants will receive ALXN2050. |
|
| Cohort 4: Healthy Control | Experimental | Participants will receive ALXN2050. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN2050 | Drug | ALXN2050 (120 milligrams) will be administered orally twice daily on Days 1 through 3, with an additional dose (120 milligrams) administered orally on the morning of Day 4. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under The Concentration-time Curve From Time 0 To The 12-hour Time Point (AUC0-12) Of Plasma ALXN2050 After Steady-state | Up to 72 hours postdose | |
| Area Under The Concentration-time Curve Calculated To The Last Observable Concentration At Time t (AUCt) Of Plasma ALXN2050 After Steady-state | Up to 72 hours postdose | |
| Maximum (Peak) Steady-state Plasma Concentration (Cmax,ss) Of Plasma ALXN2050 | Up to 72 hours postdose | |
| Time To Reach Maximum (Peak) Plasma Concentration Following ALXN2050 Administration At Steady-state (Tmax,ss) | Up to 72 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Complement Factor D Concentration At 24, 48, And 72 Hours Postdose | Baseline, 24, 48, and 72 hours postdose | |
| Change From Baseline In Plasma b Fragment Of Complement Factor B Concentration | Baseline, up to 72 hours postdose |
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Inclusion Criteria:
Body weight must be at least 50.0 kilograms (kg) and body mass index (BMI) within the range of 18.0 - 40.0 kg/meter squared (m^2) (inclusive) at the time of signing the informed consent.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Must agree to receive prophylactic antibiotics to mitigate the potential risk of meningococcal infection.
Participants with Impaired Renal Function
Aside from impaired renal function, sufficiently healthy for study participation based upon medical history, physical examination, neurological examination, laboratory tests, vital signs, and electrocardiograms (ECGs).
A clinical diagnosis of impaired stable renal function.
No clinically significant change in renal status at least 1 month prior to first dose of study intervention and is not currently or has not previously been on hemodialysis or did not have any history of peritoneal dialysis.
Stable creatinine clearance.
Must be on a stable medication regimen. Concomitant medications must be approved by Alexion unless presented in the list of common concurrent medications for participants with impaired renal function.
Matched Healthy Control Participants with Normal Renal Function
Must match the sex and the race (similar ratio of white and non-white) of participants with impaired renal function, and at screening, age must be within ± 10 years and BMI must be within ± 20% of the matching participants with impaired renal function
Healthy as determined by medical evaluation, including medical history, physical examination, neurological examination, laboratory tests, vital signs, and ECGs, and who possess a baseline eGFR ≥ 90 mL/min/1.73 m^2, based on MDRD equation at screening.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Hialeah | Florida | 33014 | United States | ||
| Clinical Trial Site |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D020742 | rhoA GTP-Binding Protein |
| ID | Term |
|---|---|
| D020741 | rho GTP-Binding Proteins |
| D020559 | Monomeric GTP-Binding Proteins |
| D019204 | GTP-Binding Proteins |
| D020558 | GTP Phosphohydrolases |
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|
| Change From Baseline In Complement Alternative Pathway Activity | Baseline, up to 72 hours postdose |
| Number Of Participants Receiving ALXN2050 With Treatment-emergent Adverse Events | Day 1 (postdose) through follow-up (30 [+/- 2] days after last study drug administration)] |
| Orlando |
| Florida |
| 32809 |
| United States |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D017766 | Acid Anhydride Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D002352 | Carrier Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D047908 | Intracellular Signaling Peptides and Proteins |