Study to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers

AUC(0-T): area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration and AUC (INF): AUC from time zero extrapolated to infinite time were measured in ng\*h/mL. Samples for the assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for midazolam with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Midazolam measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. AUC (0-T) and AUC (INF) were measured as ng\*h/mL.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

AUC(0-T): area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and AUC (INF): AUC extrapolated to infinity, were measured as ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for dextromethorphan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. The poor metabolizer of CYP2D6 was excluded from the statistical analysis. Inje cocktail components (dextromethorphan) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

AUC (0-T): area under the concentration curve from time 0 to the time of the last quantifiable concentration and AUC (INF) extrapolated to infinity were measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for losartan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (losartan) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

AUC(0-T): Area under the plasma concentration-time curve from time zero zero to the time of the last quantifiable concentration and AUC (INF): AUC extrapolated to infinity were measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for omeprazole with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (omeprazole) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. Cmax was measured in ng/mL.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Cmax was measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for dextromethorphan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. The poor metabolizer of CYP2D6 was excluded from the statistical analysis. Inje cocktail components (dextromethorphan) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for losartan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (losartan) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Cmax: Maximum observed plasma concentration was measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for omeprazole with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (omeprazole) measured using HPLC with MS/MS Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Samples for the assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for midazolam with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Cmax measured in nanograms per milliliter (ng/mL). Inje cocktail components (Midazolam) measured using High Performance Liquid Chromatography (HPLC) with Tandem Mass Spectrometry (MS/MS) Detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Participants who received any study drug and had at least 1 adequate Pharmacokinetic (PK) profile for any Inje cocktail analytes (parent or metabolite).

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. CLT/F was measured as liters/hour (L/h)

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration \[AUC(0-T)\] was measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Area under the plasma concentration-time curve from time zero extrapolated to infinite time \[AUC(INF)\] was measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Samples for assessment of plasma concentrations of Inje cocktail component metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail component metabolites were each measured using HPLC with MS/MS detection. Cmax was measured in ng/mL.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Heart Rate was taken after the participant had been sitting quietly for at least 5 minutes and was measured in beats per minute (bpm). Hear rate was taken on Day 46 (day of discharge) during the follow up period. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug.

Time frame: Baseline and Day 46 ±2 days

Population: All participants who received study drug during the treatment period and had measurements at baseline and discharge.

Heart Rate was taken after the participant had been sitting quietly for at least 5 minutes and the heart rate was measured in beats per minute (bpm). Heart Rates were obtained at screening visit, Day -1, and at 0 hour (pre-dose), 0.5 hour (post dose), and 2 hours (post dose) on Days 1, 4, 7, 11. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug.

Time frame: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11

Population: All participants who received study medication and had baseline and specific day measurement.

Systolic and Diastolic blood pressures were taken after the participant had been sitting quietly for at least 5 minutes and the pressures were measured in millimeters of mercury (mm Hg). Pressures were obtained at screening visit, Day -1, and at 0 hour (pre-dose), 0.5 hour (post dose), and 2 hours (post dose) on Days 1, 4, 7, 11. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug.

Time frame: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11

Population: All participants who received any study medication and had a baseline and specific day blood pressure measurement available.

Systolic and Diastolic blood pressures were taken after the participant had been sitting quietly for at least 5 minutes and the pressures were measured in millimeters of mercury (mm Hg). Systolic and Diastolic blood pressures were taken on Day 46 (day of discharge from the study). Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug.

Time frame: Baseline and Day 46 ±2 days

Population: All participants who had received study drug during the treatment period and had measurements at baseline and at discharge.

Adverse events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA), version 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Events captured from Day 1 (pre-dose) to last day prior to discharge (Day 46 ±2). In the total group, a participant with an AE is only counted once (ie, data reflected in Days 1, 4, 7, and 11 below could be the same participant with an AE on multiple days of the study).

Time frame: Day 1 to Day of discharge (Day 46±2)

Population: All participants who received any study medication.

Samples for laboratory tests were obtained at Screening visit, Day -1 or prior to dosing on Day 1, Days 3, 6, 10, 46 ±2, and at early termination, after 10 hours fasting. Leukocytes: \*10\^9 cells per liter (c/L) \< 0.85\*Pre-Rx if Pre-Rx \< LLN or \<0.9\*LLN if LLN \<= Pre-Rx or Pre-Rx is missing. Neutrophils (absolute): \*10\^12 c/L \< 0.85\* Pre-Rx if Pre-Rx \< 1.5, \<1.5 if Pre-Rx \>= 1.5, \< 1.5 if Pre-Rx missing. Urine blood from dipstick: \>=2 if Pre-Rx \<1 or was missing or if Pre-Rx \>=1. Urinary microscopic white blood cells (WBC) and red blood cells (RBC) \>= 2 if Pre-Rx \<2 or if Pre-Rx was missing or \>=4 if Pre-Rx \>=2.

Time frame: Day -1 to Day 46 ±2 days or at early termination

Population: Participants who received any study medication and had laboratory test results.

Samples for laboratory tests were obtained at Screening visit, Day -1 or prior to dosing on Day 1, Days 3, 6, 10, 46, and at early termination, after 10 hours fasting. Upper limits of normal (ULN); Lower limits of normal (LLN); Pre-therapy (Rx); micromoles per liter (µmol/L); millimoles per liter (mmol/L); grams per liter (g/L); Units per liter (U/L); Aspartate Aminotransferase (AST); Blood Urea Nitrogen (BUN) Total Bilirubin: \>1.1\*ULN if Pre-Rx\<= ULN or Pre-Rx is missing, or \>1.2\*Pre-Rx if Pre-Rx \>ULN. AST: \>1.25\*Pre-Rx if Pre-Rx \>ULN or 1.25\*ULN if Pre-Rx \<= ULN or Pre-Rx is missing. BUN: \>1.1\*ULN if Pre-Rx\<= ULN or Pre-Rx is missing, or \>1.2\*Pre-Rx if Pre-Rx \>ULN. Phosphorus: \<0.85\*LLN if Pre-RX \>= LLN or is missing or if Pre-Rx \< LLN. total Protein: \<0.9\*LLN if Pre-Rx\>= LLN or is missing or Pre-Rx \> LLN. Creatine Kinase: \>1.5\*Pre-Rx if Pre-Rx \> ULN or is missing or Pre-Rx is \<= ULN. Lactate Dehydrogenase: \>1.25\*ULN if Pre-Rx \<= ULN or missing, \>1.5\*Pre-Rx if Pre-Rx \> ULN.

Time frame: Day -1 to Day 46 ±2 days or at early termination

Population: Participants who received any study medication and had laboratory test results.

Participants had 12-Lead electrocardiograms (ECGs) performed at Screening Visit, Day 1 prior to dosing, Day 46 ±2, and at early termination. Definition of out-of-range: PR Interval \>210 milliseconds (msec); QRS \> 120 msec, QT \> 500 msec or \> 30 msec change from baseline (Day 1); QT with Fridericia correction (QTcF) \> 450 msec or change from baseline of \> 30 msec to \<= 60 msec or change from baseline \> 60 msec.

Time frame: Day 1 to Day 46 ±2 days or at early termination

Population: All participants who received any study medication and had an ECG performed on Day 1, Day 46 or early termination.

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. T-HALF was measured in hours (h).

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (1'-hydroxy-midazolam) to parent (midazolam) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (1'-hydroxy-midazolam) to parent (midazolam) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (5-dextrorphan ) to parent (dextromethorphan) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (5-dextrorphan) to parent (dextromethorphan) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (5-Hydroxyomeprazole) to parent (omeprazole) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (5-hydroxyomeprazole) to parent (omeprazole) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (E-3174) to parent (losartan) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (E-3174) to parent (losartan) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (paraxanthine) to parent (caffeine) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng\*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Metabolite (paraxanthine) to parent (caffeine) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and their metabolites were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Plasma half-life (T-HALF) was measured in hours (h). Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection.

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. Tmax was measured in hours (h).

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. Time of maximum observed plasma concentration (Tmax) was measured in hours (h).

Time frame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Population: Evaluable PK population: Participants who received any study drug and had at least 1 adequate PK profile for any Inje cocktail analytes (parent or metabolite).