Trial Outcomes & Findings for Safety and Efficacy of Oral AGN 203818 for the Relief of Irritable Bowel Syndrome Pain (NCT NCT00441766)

Last Updated: 2012-01-20

Results Overview

Change from baseline in mean highest-average-pain score at Week 4. The mean highest-average-pain score was the average of the 7 highest daily-average-pain scores obtained over the 14 days prior to the Week 4 visit. Patients recorded their daily-average-pain on an 11-point scale (where 0 equals no pain and 10 equals worst pain imaginable). A negative number change from baseline represents a decrease in average pain (improvement).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

213 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2012-01-20

Participant Flow

Participant milestones

Participant milestones
Measure	AGN 203818 60 mg Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo Part A: Placebo capsule every 12 hours for 4 weeks
Overall Study STARTED	53	53	53	54
Overall Study COMPLETED	39	46	44	48
Overall Study NOT COMPLETED	14	7	9	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Oral AGN 203818 for the Relief of Irritable Bowel Syndrome Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AGN 203818 60 mg n=53 Participants Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=53 Participants Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=53 Participants Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=54 Participants Part A: Placebo capsule every 12 hours for 4 weeks	Total n=213 Participants Total of all reporting groups
Age, Customized 18 to 64 years	48 participants n=5 Participants	48 participants n=7 Participants	50 participants n=5 Participants	54 participants n=4 Participants	200 participants n=21 Participants
Age, Customized >=65 years	5 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	13 participants n=21 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	53 Participants n=7 Participants	53 Participants n=5 Participants	54 Participants n=4 Participants	213 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Modified Intent-To-Treat (m-ITT). The m-ITT population included all patients who started the study (randomized), who received the study medication and had at least one post-baseline mean highest-average-pain score.

Outcome measures

Outcome measures
Measure	AGN 203818 60 mg n=47 Participants Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=50 Participants Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=50 Participants Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=50 Participants Part A: Placebo capsule every 12 hours for 4 weeks
Change From Baseline in Mean Highest-Average-Pain Score at Week 4 Baseline	5.8 Scores on a Scale Standard Deviation 1.18	5.7 Scores on a Scale Standard Deviation 1.09	6.0 Scores on a Scale Standard Deviation 1.48	6.0 Scores on a Scale Standard Deviation 1.15
Change From Baseline in Mean Highest-Average-Pain Score at Week 4 Change from Baseline at Week 4	-2.3 Scores on a Scale Standard Deviation 2.07	-1.9 Scores on a Scale Standard Deviation 1.81	-1.7 Scores on a Scale Standard Deviation 1.46	-2.2 Scores on a Scale Standard Deviation 2.15

SECONDARY outcome

Timeframe: Week 4

Percentage of patients who rated their condition as improved on the SGIC at week 4. The SGIC score was assessed using a 7-point scale (score of 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). Patients self-evaluated their overall change in symptoms (relief from symptoms of abdominal discomfort, pain, and altered bowel habits). An "improved" condition was defined as a score of 1, 2, or 3.

Outcome measures

Outcome measures
Measure	AGN 203818 60 mg n=47 Participants Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=50 Participants Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=50 Participants Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=50 Participants Part A: Placebo capsule every 12 hours for 4 weeks
Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4	76.1 Percentage of Patients	73.5 Percentage of Patients	85.7 Percentage of Patients	77.5 Percentage of Patients

SECONDARY outcome

Timeframe: Week 4

Percentage of patients who experienced AR-IBS at week 4. The AR-IBS is a self-evaluation by the patient of their perception of adequate relief of IBS pain over the last 7 days following treatment as compared to IBS pain before receiving treatment. Patients respond with either a "Yes" or "No", where "Yes" indicated adequate relief of pain and "No" indicated no relief from pain.

Outcome measures

Outcome measures
Measure	AGN 203818 60 mg n=47 Participants Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=50 Participants Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=50 Participants Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=50 Participants Part A: Placebo capsule every 12 hours for 4 weeks
Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4	60.9 Percentage of Patients	58.0 Percentage of Patients	61.2 Percentage of Patients	67.3 Percentage of Patients

SECONDARY outcome

Timeframe: Baseline, Week 4

Change from baseline in the frequency of bowel movements per day using the BSS. The BSS categorizes stool based on the patient's description of its consistency. Patients are classified into 3 IBS subtypes according to their predominant stool patterns (C=constipation; D=diarrhea; M=mixed). A positive change from baseline in the IBS-C indicates improvement and a negative change from baseline in the IBS-D and IBS-M indicates improvement.

Outcome measures

Outcome measures
Measure	AGN 203818 60 mg n=47 Participants Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=50 Participants Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=50 Participants Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=50 Participants Part A: Placebo capsule every 12 hours for 4 weeks
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-M) Change from Baseline at Week 4	-0.2 Bowel Movements (Stools) Per Day Standard Deviation 0.56	-0.3 Bowel Movements (Stools) Per Day Standard Deviation 0.68	-0.1 Bowel Movements (Stools) Per Day Standard Deviation 0.99	0.2 Bowel Movements (Stools) Per Day Standard Deviation 0.86
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-C) Baseline	0.9 Bowel Movements (Stools) Per Day Standard Deviation 0.43	1.1 Bowel Movements (Stools) Per Day Standard Deviation 0.47	1.0 Bowel Movements (Stools) Per Day Standard Deviation 0.71	0.8 Bowel Movements (Stools) Per Day Standard Deviation 0.57
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-C) Change from Baseline at Week 4	0.1 Bowel Movements (Stools) Per Day Standard Deviation 0.63	0.1 Bowel Movements (Stools) Per Day Standard Deviation 0.72	0.0 Bowel Movements (Stools) Per Day Standard Deviation 0.32	0.1 Bowel Movements (Stools) Per Day Standard Deviation 0.50
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-D) Baseline	3.5 Bowel Movements (Stools) Per Day Standard Deviation 1.59	3.6 Bowel Movements (Stools) Per Day Standard Deviation 2.95	4.3 Bowel Movements (Stools) Per Day Standard Deviation 2.48	3.4 Bowel Movements (Stools) Per Day Standard Deviation 1.88
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-D) Change from Baseline at Week 4	-0.3 Bowel Movements (Stools) Per Day Standard Deviation 1.10	-0.8 Bowel Movements (Stools) Per Day Standard Deviation 1.33	-0.7 Bowel Movements (Stools) Per Day Standard Deviation 1.09	-0.4 Bowel Movements (Stools) Per Day Standard Deviation 1.46
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) (IBS-M) Baseline	1.3 Bowel Movements (Stools) Per Day Standard Deviation 0.79	1.4 Bowel Movements (Stools) Per Day Standard Deviation 0.78	2.7 Bowel Movements (Stools) Per Day Standard Deviation 1.64	1.8 Bowel Movements (Stools) Per Day Standard Deviation 1.41

Adverse Events

AGN 203818 60 mg

Serious events: 8 serious events

Other events: 52 other events

Deaths: 0 deaths

AGN 203818 20 mg

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

AGN 203818 3 mg

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AGN 203818 60 mg n=53 participants at risk Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=53 participants at risk Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=52 participants at risk Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=54 participants at risk Part A: Placebo capsule every 12 hours for 4 weeks
Psychiatric disorders Suicide Attempt	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Psychiatric disorders Adjustment Disorder	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Metabolism and nutrition disorders Dehydration	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Hepatitis A	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Influenza	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Meningitis viral	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Viral infection	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Ear and labyrinth disorders Vertigo	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Appendicitis	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.

Other adverse events

Additional Information

Therapeutic Area Head

Allergan, Inc.

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	AGN 203818 60 mg n=53 participants at risk Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks	AGN 203818 20 mg n=53 participants at risk Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks	AGN 203818 3 mg n=52 participants at risk Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks	Placebo n=54 participants at risk Part A: Placebo capsule every 12 hours for 4 weeks
Gastrointestinal disorders Nausea	11.3% 6/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	11.3% 6/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	11.5% 6/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Abdominal Pain	9.4% 5/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Dry Mouth	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Vomiting	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Abdominal distension	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	7.4% 4/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Flatulence	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Constipation	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.6% 3/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Gastrointestinal disorders Dyspepsia	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
General disorders Fatigue	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	9.4% 5/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.6% 3/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Urinary tract infection	9.4% 5/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.8% 3/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	7.4% 4/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Infections and infestations Gastroenteritis viral	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.6% 3/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Investigations Blood bilirubin decreased	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Investigations Blood creatinine increased	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Investigations Reticulocyte count decreased	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Metabolism and nutrition disorders Anorexia	0.00% 0/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.8% 2/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Nervous system disorders Headache	7.5% 4/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.8% 3/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Nervous system disorders Somnolence	5.7% 3/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	0.00% 0/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	3.7% 2/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.
Nervous system disorders Dizziness	3.8% 2/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	9.4% 5/53 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	1.9% 1/52 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.	5.6% 3/54 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized (started the study) AND treated.