Trial Outcomes & Findings for Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis (NCT NCT02943460)

Last Updated: 2021-06-07

Results Overview

Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

First dose date up to last dose date plus 30 days (Up to 17 weeks)

Results posted on

2021-06-07

Participant Flow

Participants were enrolled at study sites in North America and Europe. The first participant was screened on 29 November 2016. The last study visit occurred on 18 May 2020.

105 participants were screened.

Participant milestones

Participant milestones
Measure	Cilofexor 100 mg Blinded Study Phase: Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97.4 weeks	Cilofexor 30 mg Blinded Study Phase: Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97 weeks	Placebo Blinded Study Phase: Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97 weeks
Blinded Study Phase STARTED	22	20	10
Blinded Study Phase COMPLETED	19	19	10
Blinded Study Phase NOT COMPLETED	3	1	0
Open Label Extension (OLE) Phase STARTED	19	18	10
Open Label Extension (OLE) Phase COMPLETED	14	11	8
Open Label Extension (OLE) Phase NOT COMPLETED	5	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cilofexor 100 mg Blinded Study Phase: Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97.4 weeks	Cilofexor 30 mg Blinded Study Phase: Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97 weeks	Placebo Blinded Study Phase: Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks Open Label Extension Phase: Cilofexor 100 mg tablet orally once daily with food for an additional up to 97 weeks
Blinded Study Phase Adverse Event	3	0	0
Blinded Study Phase Withdrew Consent	0	1	0
Open Label Extension (OLE) Phase Adverse Event	2	5	2
Open Label Extension (OLE) Phase Withdrew Consent	2	1	0
Open Label Extension (OLE) Phase Investigator's Discretion	1	1	0

Baseline Characteristics

Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cilofexor 100 mg n=22 Participants Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks	Cilofexor 30 mg n=20 Participants Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks	Placebo n=10 Participants Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks	Total n=52 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 8.6 • n=5 Participants	46 years STANDARD_DEVIATION 12.1 • n=7 Participants	42 years STANDARD_DEVIATION 10.9 • n=5 Participants	43 years STANDARD_DEVIATION 10.4 • n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	22 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	30 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	17 Participants n=5 Participants	15 Participants n=7 Participants	7 Participants n=5 Participants	39 Participants n=4 Participants
Race/Ethnicity, Customized Race · Not Permitted	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	21 Participants n=5 Participants	17 Participants n=7 Participants	9 Participants n=5 Participants	47 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Canada	4 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Austria	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment United States	12 participants n=5 Participants	17 participants n=7 Participants	7 participants n=5 Participants	36 participants n=4 Participants
Region of Enrollment United Kingdom	5 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants

PRIMARY outcome

Timeframe: First dose date up to last dose date plus 30 days (Up to 17 weeks)

Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Cilofexor 100 mg n=22 Participants Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks	Cilofexor 30 mg n=20 Participants Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks	Placebo n=10 Participants Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase	81.8 percentage of participants	70.0 percentage of participants	100.0 percentage of participants

PRIMARY outcome

Timeframe: First dose date up to last dose date plus 30 days (Up to 17 weeks)

Population: Participants in the Safety Analysis Set were analyzed.

A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.

Outcome measures

Outcome measures
Measure	Cilofexor 100 mg n=22 Participants Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks	Cilofexor 30 mg n=20 Participants Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks	Placebo n=10 Participants Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase	13.6 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: First dose date up to last dose date plus 30 days (Up to 17 weeks)

Population: Participants in the Safety Analysis Set were analyzed.

Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug in the Blinded Phase plus 30 days (and prior to or on the first dose date of the OLE phase). The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).

Outcome measures

Outcome measures
Measure	Cilofexor 100 mg n=22 Participants Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks	Cilofexor 30 mg n=20 Participants Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks	Placebo n=10 Participants Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase Grade 4	4.5 percentage of participants	5.0 percentage of participants	0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase Any Grade 1 or Higher	90.9 percentage of participants	85.0 percentage of participants	100.0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase Grade 1	22.7 percentage of participants	25.0 percentage of participants	10.0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase Grade 2	36.4 percentage of participants	35.0 percentage of participants	60.0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase Grade 3	27.3 percentage of participants	20.0 percentage of participants	30.0 percentage of participants

Adverse Events

Cilofexor 100 mg (Blinded Phase)

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Cilofexor 30 mg (Blinded Phase)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo (Blinded Phase)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Cilofexor 100 mg (Open Label Extension Phase)

Serious events: 10 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Cilofexor 100 mg (Blinded Phase) n=22 participants at risk Cilofexor 100 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily with food for up to 12.6 weeks	Cilofexor 30 mg (Blinded Phase) n=20 participants at risk Cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.7 weeks	Placebo (Blinded Phase) n=10 participants at risk Placebo to match cilofexor 30 mg tablet + placebo to match cilofexor 100 mg tablet orally once daily with food for up to 12.3 weeks	Cilofexor 100 mg (Open Label Extension Phase) n=47 participants at risk Following the Blinded Phase, eligible participants received cilofexor 100 mg tablet orally once daily for an additional up to 97.4 weeks
Gastrointestinal disorders Diarrhoea	4.5% 1/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
General disorders Chest pain	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	4.3% 2/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis sclerosing	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	4.5% 1/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Rib fracture	4.5% 1/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	4.5% 1/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/22 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/10 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.	2.1% 1/47 • Blinded Phase: First dose date up to last dose date plus 30 days (Up to 17 weeks); OLE Phase: First dose date up to last dose date plus 30 days (Up to 102 weeks) Safety Analysis Set included all participants who received at least 1 dose of study drug.