Trial Outcomes & Findings for Phase 1 Oral Solution Bioavailability Study of Apixaban When Administered Through a Nasogastric Tube in Healthy Subjects (NCT NCT02034578)

Results Overview

Samples of plasma from participants were obtained at the following times: 0 hour (h) and post dose at 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h. Apixaban was assayed using a validated Liquid chromatography tandem mass spectrometry (LC-MS/MS) method during the period of known analyte stability. Maximum observed plasma concentration (Cmax) was measured in nanograms per milliliter (ng/mL).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

75 participants

Primary outcome timeframe

Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Results posted on

2016-07-20

Participant Flow

Participants were admitted to the clinical facility on the evening prior to dosing (Day -1) and remained confined to the clinic for the duration of study.

75 enrolled; 21 randomized; 21 treated. Of the 54 not treated: 47 no longer met study criteria, 1 not needed due to adequate number of participants, 3 withdrew consent, 1 died due to substance abuse, 1 no show, 1 discharged as alternate. Study was 3-treatment crossover administered over 3 periods. ≥4 days washout after doses in Periods 1 and 2.

Participant milestones

Participant milestones
Measure	Treatment A, Then Treatment B, Then Treatment C Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.	Treatment A, Then Treatment C, Then Treatment B Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.	Treatment B, Then Treatment A, Then Treatment C Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.	Treatment B, Then Treatment C, Then Treatment A Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.	Treatment C, Then Treatment A, Then Treatment B Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.	Treatment C, Then Treatment B, Then Treatment A Treatment A: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered by mouth via oral syringe. Treatment B: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via a Nasogastric tube (NGT) immediately followed by 60 mL of dextrose 5% in water (D5W) via NGT. Treatment C: Single dose apixaban 5 mg (0.4 mg/mL oral solution x 12.5 mL) administered via an NGT immediately followed by 60 mL of infant formula via NGT. After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences across 3 periods(ABC, ACB, BAC, BCA, CAB or CBA). Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3.
Overall Study STARTED	4	3	4	3	4	3
Overall Study COMPLETED	4	3	4	3	4	3
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 1 Oral Solution Bioavailability Study of Apixaban When Administered Through a Nasogastric Tube in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5mg Apixaban n=21 Participants After a 10 hour fast, participants were randomized to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB or CBA) administered over 3 periods. Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. Treatment A was administered via oral syringe, Treatment B was administered via an NGT followed by 60 mL of D5W via an NGT, and Treatment C was administered via an NGT, followed by 60 mL of infant formula via an NGT. There was at least a 4 day washout before receiving the next scheduled treatment in the next period.
Age, Continuous	33 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Population: All participants who received study drug and had adequate PK profiles were included in the analysis.

Samples of plasma from participants were obtained at the following times: 0 hour (h) and post dose at 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h. Apixaban was assayed using a validated Liquid chromatography tandem mass spectrometry (LC-MS/MS) method during the period of known analyte stability. Maximum observed plasma concentration (Cmax) was measured in nanograms per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban	190.873 ng/mL Interval 176.032 to 206.965	181.862 ng/mL Interval 162.834 to 203.112	153.693 ng/mL Interval 140.686 to 167.904

SECONDARY outcome

Timeframe: Day 1 to Day 12

Population: All participants who received study drug were analyzed.

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.

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death Discontinuation Due to AE	0 participants	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death SAE	0 participants	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death Death	0 participants	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death Adverse Events	2 participants	4 participants	3 participants

SECONDARY outcome

Timeframe: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Samples of plasma from participants were obtained at the following times: 0 hour (h), 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. Maximum observed plasma concentration (Tmax) was measured in hours (h).

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban	0.517 h Interval 0.48 to 2.0	1.000 h Interval 0.3 to 2.0	1.00 h Interval 0.48 to 2.0

SECONDARY outcome

Timeframe: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Population: All participants who received study drug and had adequate PK profiles were included in the analysis.

Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-T) was measured in nanograms\*hours per milliliter (ng\*h/mL).

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban	1269.784 ng*h/mL Interval 1140.0 to 1414.343	1226.339 ng*h/mL Interval 1064.999 to 1412.121	1166.572 ng*h/mL Interval 1031.549 to 1319.268

SECONDARY outcome

Timeframe: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Population: All participants who received study drug and had adequate PK profiles were included in the analysis.

Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-INF) was measured in ng\*h/mL.

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban	1292.775 ng*h/mL Interval 1161.691 to 1438.65	1250.913 ng*h/mL Interval 1088.38 to 1437.718	1192.387 ng*h/mL Interval 1056.6 to 1345.624

SECONDARY outcome

Timeframe: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3

Population: All participants who received study drug and had adequate PK profiles were included in the analysis.

Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. T-HALF was measured in hours (h).

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Mean Plasma Elimination Half-Life (T-HALF) of Apixaban	10.5 h Standard Deviation 4.2	10.4 h Standard Deviation 4.5	10.6 h Standard Deviation 3.8

SECONDARY outcome

Timeframe: Screening, Day 1 of Periods, 1, 2, and 3, and Day 4 of Period 3

Population: All participants who received study drug were analyzed.

12-lead electrocardiograms (ECGs) and Vital Signs were performed at Screening, and Day 1 of Periods 1, 2 and 3 (pre-dose and prior to NGT placement, if done). Vital signs and ECGs were also performed on Day 4 of Period 3, prior to discharge from the study. Vital signs included body temperature, respiratory rate, seated blood pressure and heart rate. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. Participants had physical examinations on Period 1, Day 1 (pre-dose) and Day 4 of Period 3, prior to study discharge.

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 Participants Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings ECG	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings Vital Signs	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings Physical Examination	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Screening, Day -1, Day 4 of Periods, 1, 2, and 3

Population: Participants who received study drug were analyzed.

Participants were required to fast for at least 10 hours prior to the collection of specimens for clinical laboratory tests. Tests were performed at Screening, Day -1, and Day 4 of each period 1 - 3. Leukocyte criteria: Lower limits of normal (LLN), upper limits of normal (ULN), pre-treatment (preRX). Low Leukocytes: if value \< 0.9\*LLN, or if preRX \< LLN then use \< 0.85\* preRX. High lymphocytes: if value \> 7.500 10\^3 cells/ µL. Low neutrophils plus bands: if value \<= 1.500 10\^3 cells/µL. High creatine kinase: if value \> 1.5\* ULN. Blood in urine: if value \>= 2 plus, or if preRX \>= 1 plus then use \>= 2\*preRX.

Outcome measures

Outcome measures
Measure	5mg Apixaban Via Oral Syringe (A) n=21 Participants Single dose Apixaban 5 mg oral solution via oral syringe	5mg Apixaban Via NGT Followed by D5W (B) Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of D5W via NGT	5 mg Apixaban Via NGT Followed by Infant Formula (C) Single dose Apixaban 5 mg oral solution via NGT immediately followed by 60 mL of infant formula via NGT
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests Low Leukocytes	1 participants	—	—
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests High Lymphocytes	1 participants	—	—
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests Low Neutrophils plus bands	5 participants	—	—
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests High Creatine Kinase	1 participants	—	—
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests Blood in Urine	1 participants	—	—

Adverse Events

5mg Apixaban Via Oral Syringe (A)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

5mg Apixaban Via NGT Followed by D5W (B)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

5 mg Apixaban Via NGT Followed by Infant Formula (C)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	5mg Apixaban Via Oral Syringe (A) n=21 participants at risk After a 10 hour fast, on Day 1 of Period 1, participants were randomized to one of six treatment sequences administered over 3 Periods (ABC, ACB, BAC, BCA, CAB or CBA) and received a single dose of apixaban 5 mg. After participants received the Period 1 dose, there was ≥4-days of washout before their Period 2, Day 1 dose was administered, which was followed by another ≥4-days of washout. After their Period 3, Day 1 dose, participants were discharged on Day 4 of Period 3. In Treatment A the single dose of 5 mg apixaban was administered via oral syringe.	5mg Apixaban Via NGT Followed by D5W (B) n=21 participants at risk In Treatment B the single dose of 5 mg apixaban was administered via nasogastric tube (NGT) followed by 60 mL of dextrose, water (D5W) via the NGT.	5 mg Apixaban Via NGT Followed by Infant Formula (C) n=21 participants at risk In Treatment C, the single dose of 5 mg apixaban was administered via NGT, followed by 60 mL of infant formula via the NGT.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Respiratory, thoracic and mediastinal disorders Throat Irritation	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Gastrointestinal disorders Abdominal Pain	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Nervous system disorders Headache	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Eye disorders Eyelid Oedema	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	4.8% 1/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.	0.00% 0/21 • Day 1 to Day 12 All participants who received at least one dose of study drug were analyzed.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trials primary publication.
Publication restrictions are in place

Restriction type: OTHER