Trial Outcomes & Findings for Combination Obeticholic Acid (OCA) and Statins for Monitoring of Lipids (CONTROL) (NCT NCT02633956)

Last Updated: 2018-06-04

Results Overview

The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed nonalcoholic steatohepatitis (NASH) and the ability of atorvastatin to modulate this effect as measured by change (least squares mean) from baseline at week 16 in LDL concentration

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

84 participants

Primary outcome timeframe

Baseline and Week 16

Results posted on

2018-06-04

Participant Flow

Subjects using statins within 30 days of the initial Screening visit (Screening Visit 1) are required to stop statin therapy immediately following this initial visit and must undergo a 4-week statin washout period prior to Screening Visit 2.

Participant milestones

Participant milestones
Measure	5 mg Obeticholic Acid 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
Overall Study STARTED	20	21	22	21
Overall Study COMPLETED	19	19	20	21
Overall Study NOT COMPLETED	1	2	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Obeticholic Acid (OCA) and Statins for Monitoring of Lipids (CONTROL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 mg Obeticholic Acid n=20 Participants 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=21 Participants 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=22 Participants 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=21 Participants One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)	Total n=84 Participants Total of all reporting groups
Age, Continuous	52.9 years STANDARD_DEVIATION 10.13 • n=5 Participants	57.1 years STANDARD_DEVIATION 11.62 • n=7 Participants	62.2 years STANDARD_DEVIATION 11.06 • n=5 Participants	59.8 years STANDARD_DEVIATION 9.88 • n=4 Participants	58.1 years STANDARD_DEVIATION 11.07 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	51 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants	8 Participants n=4 Participants	33 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	17 Participants n=4 Participants	64 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	20 Participants n=7 Participants	19 Participants n=5 Participants	16 Participants n=4 Participants	74 Participants n=21 Participants
Race (NIH/OMB) More than one race	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
Race (NIH/OMB) Unknown or Not Reported	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
Fibrosis stage (NASH Clinical Research Network (CRN) categories) Stage 1 and 2	10 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	41 Participants n=21 Participants
Fibrosis stage (NASH Clinical Research Network (CRN) categories) Stage 3 and 4	10 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	43 Participants n=21 Participants
Screening LDL Less than or equal 125 mg/dL	11 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	46 Participants n=21 Participants
Screening LDL Greater than 125 mg/dL	9 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	38 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Efficacy evaluable population

Outcome measures

Outcome measures
Measure	5 mg Obeticholic Acid n=13 Participants 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 Visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=17 Participants 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=18 Participants 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=19 Participants One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
The Effect of Obeticholic Acid on Low-density Lipoprotein (LDL) Concentration (Least Squares Mean Change From Baseline at Week 16)	-33.2 mg/dL Standard Error 4.93	-44.27 mg/dL Standard Error 4.10	-39.54 mg/dL Standard Error 4.24	-53.33 mg/dL Standard Error 3.93

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Efficacy evaluable population

The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed NASH and the ability of atorvastatin to modulate this effect as measured by change from baseline (least squares mean) at week 16 in LDL particle size. It is LDL particle diameter size (nm) that is reported.

Outcome measures

Outcome measures
Measure	5 mg Obeticholic Acid n=12 Participants 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 Visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=17 Participants 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=17 Participants 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=17 Participants One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
The Effect of Obeticholic Acid on LDL Particle Size (Least Squares Mean Change From Baseline at Week 16)	0.02 nm Standard Error 0.15	-0.41 nm Standard Error 0.12	-0.09 nm Standard Error 0.12	-0.49 nm Standard Error 0.12

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Efficacy evaluable population

The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed nonalcoholic NASH and the ability of atorvastatin to modulate this effect as measured by change (least squares mean) from baseline at week 16 in LDL particle concentration (total)

Outcome measures

Outcome measures
Measure	5 mg Obeticholic Acid n=12 Participants 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 Visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=17 Participants 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=17 Participants 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=19 Participants One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
The Effect of Obeticholic Acid on LDL Particle Concentration (Total) (Least Squares Mean Change From Baseline at Week 16)	-224.79 nmol/L Standard Error 62.58	-325.04 nmol/L Standard Error 49.81	-336.22 nmol/L Standard Error 51.40	-439.84 nmol/L Standard Error 47.70

Adverse Events

5 mg Obeticholic Acid

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

10 mg Obeticholic Acid

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

25 mg Obeticholic Acid

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	5 mg Obeticholic Acid n=20 participants at risk 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=21 participants at risk 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=22 participants at risk 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=21 participants at risk One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
Hepatobiliary disorders Cholecystitis	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage IV	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Vascular disorders Hypertensive crisis	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks

Other adverse events

Additional Information

Medical Information

Intercept Pharmaceuticals, Inc

Phone: 844-782-4278

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigators must wait 18 months after the study end to publish their results and a multi-center publication must come first. The sponsor has a 45 day review period with the option to extend to an additional 90 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	5 mg Obeticholic Acid n=20 participants at risk 5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	10 mg Obeticholic Acid n=21 participants at risk 10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	25 mg Obeticholic Acid n=22 participants at risk 25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Obeticholic Acid: Once a day (QD) by mouth (PO) Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.	Placebo n=21 participants at risk One tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg. Atorvastatin: Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated. Placebo: Once a day (QD) by mouth (PO)
Skin and subcutaneous tissue disorders Pruritus	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	54.5% 12/22 • Number of events 19 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	18.2% 4/22 • Number of events 4 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	14.3% 3/21 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Musculoskeletal and connective tissue disorders Myalgia	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.1% 2/22 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Constipation	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	13.6% 3/22 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Diarrhoea	10.0% 2/20 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.1% 2/22 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	14.3% 3/21 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Abdominal distension	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Flatulence	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Dyspepsia	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Gastrointestinal disorders Nausea	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.1% 2/22 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Infections and infestations Urinary tract infection	15.0% 3/20 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Infections and infestations Upper respiratory tract infection	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Infections and infestations Bronchitis	0.00% 0/20 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.1% 2/22 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Infections and infestations Sinusitis	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.5% 2/21 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Nervous system disorders Headache	15.0% 3/20 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.5% 1/22 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Nervous system disorders Hypoaesthesia	10.0% 2/20 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
General disorders Fatigue	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	14.3% 3/21 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	13.6% 3/22 • Number of events 3 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Investigations Weight increased	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Injury, poisoning and procedural complications Ligament sprain	5.0% 1/20 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks	9.1% 2/22 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/21 • From time of first dose to end of double-blind phase participation, up to 16 weeks
Respiratory, thoracic and mediastinal disorders Cough	10.0% 2/20 • Number of events 2 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks	0.00% 0/22 • From time of first dose to end of double-blind phase participation, up to 16 weeks	4.8% 1/21 • Number of events 1 • From time of first dose to end of double-blind phase participation, up to 16 weeks