Trial Outcomes & Findings for Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD (NCT NCT04247594)

NCT ID: NCT04247594

Last Updated: 2023-11-21

Results Overview

Treatment emergent AEs including SAEs

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: approximately 300 days
• Results posted on: 2023-11-21

Participant Flow

Each individual was provided with oral and written information describing the nature, purpose and duration of the study, participation/termination conditions, and risks and benefits. Prior to initiation of any study-related procedures, subjects signed and dated the ICF to participate in the study.

All patients completed the following study procedures prior to a confirmation of eligibility: Signed Informed Consent Form, Review inclusion/exclusion criteria, Medication and Medical History, Height/Weight/ BMI, Vital signs, ECG (12-lead) in triplicate, Physical examination, Serum pregnancy test (females of child-bearing potential only) and so on.

Participant milestones

Measure	Open Label Participants will receive progressively higher doses of voxelotor administration starting from 1500 mg Voxelotor: synthetic small molecule supplied as 500 mg tablets
Overall Study STARTED	6
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Open Label Participants will receive progressively higher doses of voxelotor administration starting from 1500 mg Voxelotor: synthetic small molecule supplied as 500 mg tablets
Overall Study Withdrawal by Subject	4

Baseline Characteristics

Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD

Baseline characteristics by cohort

Measure	Open Label n=6 Participants Participants will receive progressively higher doses of voxelotor administration starting from 1500 mg Voxelotor: synthetic small molecule supplied as 500 mg tablets
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	32 Years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	6 Participants n=5 Participants
Weight	66.45 kg n=5 Participants
Height	171 cm n=5 Participants
Body Mass Index (BMI)	22 kg/m^2 n=5 Participants

PRIMARY outcome

Timeframe: approximately 300 days

Population: Subjects treated with at least one dose of voxelotor

Treatment emergent AEs including SAEs

Outcome measures

Measure	Voxelotor 1500 mg n=6 Participants Participants received 1500 mg voxelotor per day for 3 weeks in Period 1.	Voxelotor 2000 mg n=4 Participants Participants received 2000 mg voxelotor per day for 3 weeks in Period 2.	Voxelotor 2500 mg n=3 Participants Participants received 2500 mg voxelotor per day for 3 weeks in Period 3.	Voxelotor 3000 mg n=1 Participants Participants received 3000 mg voxelotor per day for 3 weeks in Period 4.
Treatment-emergent Adverse Events (AEs) Sickle cell disease (SCD) related TEAE	5 Participants	1 Participants	1 Participants	0 Participants
Treatment-emergent Adverse Events (AEs) Non-SCD related TEAE	6 Participants	4 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: approximately 200 days

Population: Subjects treated with at least one dose of Voxelotor

Outcome measures

Measure	Voxelotor 1500 mg n=6 Participants Participants received 1500 mg voxelotor per day for 3 weeks in Period 1.	Voxelotor 2000 mg n=4 Participants Participants received 2000 mg voxelotor per day for 3 weeks in Period 2.	Voxelotor 2500 mg n=3 Participants Participants received 2500 mg voxelotor per day for 3 weeks in Period 3.	Voxelotor 3000 mg n=1 Participants Participants received 3000 mg voxelotor per day for 3 weeks in Period 4.
Number of Participants With Clinically Significant Abnormalities in Hb, Unconjugated Bilirubin, % Reticulocyte, Absolute Reticulocyte, and Lactate Dehydrogenase [LDH]	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: approximately 200 days

Population: Subjects treated with at least one dose of Voxelotor

Participants with an Hb increase > 1 g/dL compared to Baseline.

Outcome measures

Measure	Voxelotor 1500 mg n=6 Participants Participants received 1500 mg voxelotor per day for 3 weeks in Period 1.	Voxelotor 2000 mg Participants received 2000 mg voxelotor per day for 3 weeks in Period 2.	Voxelotor 2500 mg Participants received 2500 mg voxelotor per day for 3 weeks in Period 3.	Voxelotor 3000 mg Participants received 3000 mg voxelotor per day for 3 weeks in Period 4.
Number of Participants With an Hb Increase > 1 g/dL Compared to Baseline	0 Participants	—	—	—

SECONDARY outcome

Timeframe: approximately 200 days

Population: Subjects treated with at least one dose of Voxelotor

Incidence rate of vaso-occlusive crisis

Outcome measures

Measure	Voxelotor 1500 mg n=6 Participants Participants received 1500 mg voxelotor per day for 3 weeks in Period 1.	Voxelotor 2000 mg Participants received 2000 mg voxelotor per day for 3 weeks in Period 2.	Voxelotor 2500 mg Participants received 2500 mg voxelotor per day for 3 weeks in Period 3.	Voxelotor 3000 mg Participants received 3000 mg voxelotor per day for 3 weeks in Period 4.
Incidence Rate of VOCs	0 Participants	—	—	—

Adverse Events

Period 1

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Period 2

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Period 3

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Period 4

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Period 1 n=6 participants at risk 1500 mg per day	Period 2 n=4 participants at risk 2000 mg per day	Period 3 n=3 participants at risk 2500 mg per day	Period 4 n=1 participants at risk 3000 mg per day
Blood and lymphatic system disorders Sickle cell anaemia with crisis	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	33.3% 1/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Reproductive system and breast disorders Priapism	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.

Other adverse events

Measure	Period 1 n=6 participants at risk 1500 mg per day	Period 2 n=4 participants at risk 2000 mg per day	Period 3 n=3 participants at risk 2500 mg per day	Period 4 n=1 participants at risk 3000 mg per day
Investigations Alanine aminotransferase increased	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	66.7% 2/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Nervous system disorders Headache	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	50.0% 2/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	33.3% 1/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
General disorders Fatigue	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Abdominal pain upper	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Constipation	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Diarrhoea	66.7% 4/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Dry mouth	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	33.3% 1/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Nausea	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Skin and subcutaneous tissue disorders Pruritus allergic	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Infections and infestations Urinary tract infection	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	100.0% 1/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	66.7% 2/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Abdominal Distension	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Dental caries	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Oral Pain	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Rectal haemorrhage	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Vomiting	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
General disorders Influenza like illness	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
General disorders Malaise	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
General disorders Non-Cardiac Chest Pain	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Infections and infestations Conjunctivitis	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Infections and infestations Tonsillitis	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Nervous system disorders Lethargy	16.7% 1/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	33.3% 1/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	50.0% 3/6 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	25.0% 1/4 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/3 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.	0.00% 0/1 • All adverse events were recorded from the time the study participant signs the informed consent form (ICF) until 28 days after the last dose of study drug (up to approximately 300 days) Adverse events were coded using the Medical Dictionary for Regulatory Activities Dictionary (MedDRA) version 24.0 and were categorized by system organ class (SOC) and preferred term (PT). National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 was used to determine the grade.

Additional Information

Eleanor Lisbon

Global Blood Therapeutics, Inc.

Phone: +1 913 449 4319

Email: elisbon@gbt.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place