Table 2.
Schedule of key study assessments in the NEUTRALIZE study
| Procedure | Screening | Open-label phase | Randomized phase (visit 2 or 3–7) | Follow-up | |||||
|---|---|---|---|---|---|---|---|---|---|
| Visit | 1 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Study day | 1 | 1 | 2 | 2 or 3 | 8 (±1) | 15 (±1) | 22 (±1) | 29 (±1) | 36 (±3) |
| Routine clinical procedures | |||||||||
| Demographics | X | ||||||||
| Physical exam | X | X | |||||||
| Medical history | X | ||||||||
| Concomitant medications | At every visit and may be conducted by phone (if not part of a visit) | ||||||||
| Vital signs | X | X | X | X | X | X | X | ||
| Weight | X | X | X | X | X | X | X | ||
| Routine safety measurements | |||||||||
| AEs | At every visit and may be conducted by phone (if not part of a visit) | ||||||||
| Urine pregnancy test | X | ||||||||
| Clinical safety laboratory testsa | X | X | X | X | |||||
| ECG | X | X | X | X | |||||
| Efficacy laboratory measurementsb | |||||||||
| Central laboratory K+, HCO3–, Cl– | (X)c | (X)c | X | X | X | (X)c | (X)c | ||
| i-STAT testsd | X, X | X | X | X | X | X | X | X | |
| Spot urine testse | X | X | X | X | X | X | X | ||
| Serum aldosterone | X | X | X | X | |||||
| Optional genomics blood sample | X | ||||||||
| Study drug administration | |||||||||
| Drug dispensation (open-label phase) | X | X | |||||||
| Drug dispensation (randomized phase) | X | X | X | X | |||||
| Randomization | X | ||||||||
| Dose titration (if needed) | X | X | X | ||||||
AE, adverse event; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Ca2+, calcium; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; Cl–, chloride; CO2, carbon dioxide; ECG, electrocardiography; eGFR, estimated glomerular filtration rate; HCO3–, bicarbonate; K+, potassium; Mg2+, magnesium; Na+, sodium; NH4+, ammonium; PO4, phosphate; UACR, urinary albumin-to-creatinine ratio.
Includes hematology (hemoglobin, hematocrit, leukocyte count, and platelet count), urinalysis by dipstick (urinary hemoglobin/erythrocytes/blood, protein/albumin, and glucose), and serum chemistry (serum Na+, K+, HCO3– [total CO2], Cl–, glucose, creatinine, BUN, BUN-to-creatinine ratio, eGFR [using CKD-EPI formula], anion gap [blood from i-STAT], albumin, total protein, Ca2+, Mg2+, PO4, total bilirubin, ALP, ALT, and AST).
Measurements are taken after the patient has fasted for 4 h (meals can transiently change acid-base status).
When measured on Visits 1, 3, 7, and 8, these results were also included as part of the clinical safety assessment.
Includes HCO3– as total CO2, K+, creatinine, and anion gap; at screening, 2 measurements will be taken 1 h (±15 min) apart.
Central laboratory measurement of urinary albumin, NH4+, citrate, pH, and creatinine, and calculated anion gap (based on urinary Na+, K+, and Cl–), UACR, and NH4+-to-creatinine ratio.