Trial Outcomes & Findings for Efficacy and Safety of Colesevelam in Pediatric Patients With Genetic High Cholesterol (NCT NCT00145574)

NCT ID: NCT00145574

Last Updated: 2010-04-15

Results Overview

Percent change in LDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline)to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 194 participants
• Primary outcome timeframe: 8 weeks (week 8 - day 1)
• Results posted on: 2010-04-15

Participant Flow

Study was conducted at 41 clinical sites; Australia (1 site), Austria (1 site), Canada (5 sites), Hungary (1 site), Israel (5 sites), New Zealand (1 site), Norway (2 sites), Slovakia (3 sites), South Africa (4 sites), Czech Republic (3 sites), Netherlands (2 sites), and USA (13 sites). Study initiated November 5, 2005 completed December 18, 2007.

Period I Run-In (4 weeks): Period I was a single-blind stabilization period prior to randomization. All subjects received 6 placebo tablets daily. Objective was to evaluate dosing compliance and tolerability to the tablets prior to randomization. Subjects could be on stable pediatric approved statin regimen and low cholesterol diet for 6 weeks.

Participant milestones

Measure	Placebo Placebo similar to active	Low Dose Colesevelam Low dose colesevelam 1.9 grams per day	High Dose Colesevelam High dose colesevelam 3.8 grams per day
Double Blind STARTED	65	65	64
Double Blind COMPLETED	64	60	62
Double Blind NOT COMPLETED	1	5	2
Open Label Long-term Extension STARTED	0	0	184
Open Label Long-term Extension COMPLETED	0	0	173
Open Label Long-term Extension NOT COMPLETED	0	0	11

Reasons for withdrawal

Measure	Placebo Placebo similar to active	Low Dose Colesevelam Low dose colesevelam 1.9 grams per day	High Dose Colesevelam High dose colesevelam 3.8 grams per day
Double Blind Adverse Event	0	3	1
Double Blind Withdrawal by Subject	1	1	1
Double Blind required restricted medicine	0	1	0
Open Label Long-term Extension Adverse Event	0	0	5
Open Label Long-term Extension Lost to Follow-up	0	0	1
Open Label Long-term Extension Withdrawal by Subject	0	0	4
Open Label Long-term Extension required restricted medicine	0	0	1

Baseline Characteristics

Efficacy and Safety of Colesevelam in Pediatric Patients With Genetic High Cholesterol

Baseline characteristics by cohort

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=65 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=64 Participants High dose colesevelam 3.8 grams per day	Total n=194 Participants Total of all reporting groups
Age, Categorical <=18 years	65 Participants n=5 Participants	65 Participants n=7 Participants	64 Participants n=5 Participants	194 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age Continuous	14.3 years STANDARD_DEVIATION 1.74 • n=5 Participants	14.1 years STANDARD_DEVIATION 2.19 • n=7 Participants	13.9 years STANDARD_DEVIATION 2.0 • n=5 Participants	14.1 years STANDARD_DEVIATION 1.98 • n=4 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	26 Participants n=7 Participants	24 Participants n=5 Participants	71 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	39 Participants n=7 Participants	40 Participants n=5 Participants	123 Participants n=4 Participants
Region of Enrollment United States	16 participants n=5 Participants	14 participants n=7 Participants	15 participants n=5 Participants	45 participants n=4 Participants
Region of Enrollment Canada	7 participants n=5 Participants	9 participants n=7 Participants	7 participants n=5 Participants	23 participants n=4 Participants
Region of Enrollment Austria	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment South Africa	18 participants n=5 Participants	16 participants n=7 Participants	17 participants n=5 Participants	51 participants n=4 Participants
Region of Enrollment Israel	6 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment Norway	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Netherlands	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Hungary	6 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment New Zealand	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Slovakia	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants
Region of Enrollment Czech Republic	2 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	10 participants n=4 Participants
Statin Status non-naive	48 participants n=5 Participants	50 participants n=7 Participants	49 participants n=5 Participants	147 participants n=4 Participants
Statin Status naive	17 participants n=5 Participants	15 participants n=7 Participants	15 participants n=5 Participants	47 participants n=4 Participants
Tanner Stage I	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Tanner Stage II	9 participants n=5 Participants	15 participants n=7 Participants	15 participants n=5 Participants	39 participants n=4 Participants
Tanner Stage III	20 participants n=5 Participants	16 participants n=7 Participants	16 participants n=5 Participants	52 participants n=4 Participants
Tanner Stage IV	23 participants n=5 Participants	19 participants n=7 Participants	20 participants n=5 Participants	62 participants n=4 Participants
Tanner Stage V	13 participants n=5 Participants	15 participants n=7 Participants	13 participants n=5 Participants	41 participants n=4 Participants
Body Mass Index	21.9 kg/m2 STANDARD_DEVIATION 4.30 • n=5 Participants	23.4 kg/m2 STANDARD_DEVIATION 6.14 • n=7 Participants	22.2 kg/m2 STANDARD_DEVIATION 4.75 • n=5 Participants	22.5 kg/m2 STANDARD_DEVIATION 5.14 • n=4 Participants
height	164.8 cm STANDARD_DEVIATION 10.35 • n=5 Participants	160.7 cm STANDARD_DEVIATION 10.90 • n=7 Participants	162.1 cm STANDARD_DEVIATION 11.94 • n=5 Participants	162.5 cm STANDARD_DEVIATION 11.16 • n=4 Participants
weight	60.3 kg STANDARD_DEVIATION 15.32 • n=5 Participants	61.5 kg STANDARD_DEVIATION 20.77 • n=7 Participants	59.0 kg STANDARD_DEVIATION 16.81 • n=5 Participants	60.3 kg STANDARD_DEVIATION 17.72 • n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward.

Percent change in LDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline)to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=63 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=63 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Low Density Lipoprotein-cholesterol (LDL-C) From Day 1 (Study Baseline) to Week 8.	2.9 percent change from baseline Standard Deviation 16.46	-3.7 percent change from baseline Standard Deviation 18.36	-10.6 percent change from baseline Standard Deviation 19.36	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward.

Percent change in total cholesterol (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=63 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=63 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Total Cholesterol (TC) From Day 1 (Study Baseline) to Week 8.	2.9 percent change from baseline Standard Deviation 13.29	-1.1 percent change from baseline Standard Deviation 14.22	-5.4 percent change from baseline Standard Deviation 15.8	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward.

Percent change in triglycerides (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=63 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=63 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Triglycerides (TG) From Day 1 (Study Baseline) to Week 8.	12.5 percent change from baseline Standard Deviation 40.8	16.9 percent change from baseline Standard Deviation 35.7	12.5 percent change from baseline Standard Deviation 53.2	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward.

Percent change in HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=63 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=63 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma High-density Lipoprotein-cholesterol (HDL-C) From Day 1 (Study Baseline) to Week 8.	2.5 percent change from baseline Standard Deviation 12.52	3.9 percent change from baseline Standard Deviation 12.45	8.5 percent change from baseline Standard Deviation 14.72	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward.

Percent change in non-HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=65 Participants Placebo similar to active	Low Dose Colesevelam n=63 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=63 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Non-high Density Lipoprotein-cholesterol (Non-HDL-C) From Day 1 (Study Baseline) to Week 8.	3.4 percent change from baseline Standard Deviation 16.01	-2.1 percent change from baseline Standard Deviation 17.32	-8.4 percent change from baseline Standard Deviation 18.28	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat (ITT) Population in Double blind Period. Last Observation Carried Forward.

Percent change in Apolipoprotien A-I (Apo A-1) (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=63 Participants Placebo similar to active	Low Dose Colesevelam n=62 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=61 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Apolipoprotien A-I (Apo A-1) From Day 1 (Study Baseline) to Week 8.	4.4 percent change from baseline Standard Deviation 14.62	7.0 percent change from baseline Standard Deviation 13.96	11.2 percent change from baseline Standard Deviation 16.79	—

SECONDARY outcome

Timeframe: 8 weeks (week 8 - day 1)

Population: Intent-to-Treat (ITT) Population in Double blind Period. Last Observation Carried Forward.

Percent change in Apo B (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.

Outcome measures

Measure	Placebo n=63 Participants Placebo similar to active	Low Dose Colesevelam n=62 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=61 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Plasma Apolipoprotein B (Apo B) From Day 1 (Study Baseline) to Week 8.	2.3 percent change from baseline Standard Deviation 14.78	-0.7 percent change from baseline Standard Deviation 16.52	-7.0 percent change from baseline Standard Deviation 14.45	—

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent-to-Treat (ITT) Population. Last Observation Carried Forward.

Percent change in low-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=62 Participants Placebo similar to active	Low Dose Colesevelam n=56 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=60 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=178 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Study Baseline (Day 1) to Week 26.	-11.9 percent change from baseline Standard Deviation 22.39	-16.8 percent change from baseline Standard Deviation 19.85	-13.5 percent change from baseline Standard Deviation 21.58	-14.0 percent change from baseline Standard Deviation 21.32

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in total cholesterol (TC) from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=62 Participants Placebo similar to active	Low Dose Colesevelam n=56 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=60 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=178 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Total Cholesterol From Study Baseline (Day 1) to Week 26.	-7.5 percent change from baseline Standard Deviation 17.21	-9.1 percent change from baseline Standard Deviation 16.91	-7.5 percent change from baseline Standard Deviation 17.55	-8.0 percent change from baseline Standard Deviation 17.15

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in triglycerides from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=62 Participants Placebo similar to active	Low Dose Colesevelam n=56 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=60 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=178 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Triglycerides From Study Baseline (Day 1) to Week 26.	-5.3 percent change from baseline Standard Deviation 59.1	19.5 percent change from baseline Standard Deviation 58.0	14.2 percent change from baseline Standard Deviation 64.5	11.5 percent change from baseline Standard Deviation 61.8

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=62 Participants Placebo similar to active	Low Dose Colesevelam n=56 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=60 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=178 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Study Baseline (Day 1) to Week 26.	6.6 percent change from baseline Standard Deviation 13.64	8.5 percent change from baseline Standard Deviation 20.33	9.3 percent change from baseline Standard Deviation 19.37	8.1 percent change from baseline Standard Deviation 17.86

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in non-high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=61 Participants Placebo similar to active	Low Dose Colesevelam n=56 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=60 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=177 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Non-high-density Lipoprotein Cholesterol From Study Baseline (Day 1) to Week 26.	-10.0 percent change from baseline Standard Deviation 21.04	-13.2 percent change from baseline Standard Deviation 19.9	-11.0 percent change from baseline Standard Deviation 20.80	-11.3 percent change from baseline Standard Deviation 20.53

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in apolipoprotein A-I from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=52 Participants Placebo similar to active	Low Dose Colesevelam n=52 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=57 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=161 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Apolipoprotein A-I From Study Baseline (Day 1) to Week 26.	4.7 percent change from baseline Standard Deviation 12.95	4.9 percent change from baseline Standard Deviation 14.86	7.2 percent change from baseline Standard Deviation 15.34	5.6 percent change from baseline Standard Deviation 14.40

SECONDARY outcome

Timeframe: 26 weeks (week 26 - day 1)

Population: Intent to treat population. Last Observation Carried Forward.

Percent change in apolipoprotein B from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.

Outcome measures

Measure	Placebo n=52 Participants Placebo similar to active	Low Dose Colesevelam n=52 Participants Low dose colesevelam 1.9 grams per day	High Dose Colesevelam n=57 Participants High dose colesevelam 3.8 grams per day	All High Dose Colesevelam in Open Label Extension n=161 Participants Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose).
Percent Change in Apolipoprotein B From Study Baseline (Day 1) to Week 26.	-11.4 percent change from baseline Standard Deviation 16.86	-11.3 percent change from baseline Standard Deviation 18.71	-11.2 percent change from baseline Standard Deviation 17.86	-11.3 percent change from baseline Standard Deviation 17.72

Adverse Events

Placebo Double Blind Period

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Low Dose Colesevelam Double Blind Period

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

High Dose Colesevelam Double Blind Period

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

High Dose Colesevelam Open Label Extension

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Double Blind Period n=65 participants at risk Placebo taken from day 1 to week 8.	Low Dose Colesevelam Double Blind Period n=65 participants at risk Low dose colesevelam 1.9 grams per day taken from day 1 to week 8.	High Dose Colesevelam Double Blind Period n=64 participants at risk High dose colesevelam 3.8 grams per day taken from day 1 to week 8.	High Dose Colesevelam Open Label Extension n=184 participants at risk All participants of the Open Label Extension (weeks 8-26) took colesevelam 3.8 grams per day.
Skin and subcutaneous tissue disorders contusion	0.00% 0/65	1.5% 1/65 • Number of events 1	0.00% 0/64	0.00% 0/184
Congenital, familial and genetic disorders renal hypoplasia	0.00% 0/65	1.5% 1/65 • Number of events 1	0.00% 0/64	0.00% 0/184
Gastrointestinal disorders gastroesophageal reflux disease	1.5% 1/65 • Number of events 1	0.00% 0/65	0.00% 0/64	0.00% 0/184
Injury, poisoning and procedural complications poisoning deliberate	1.5% 1/65 • Number of events 1	0.00% 0/65	0.00% 0/64	0.00% 0/184
Blood and lymphatic system disorders idiopathic thrombocytopenic purpura	1.5% 1/65 • Number of events 1	0.00% 0/65	0.00% 0/64	0.00% 0/184
Neoplasms benign, malignant and unspecified (incl cysts and polyps) nasopharyngeal cancer NOS	0.00% 0/65	1.5% 1/65 • Number of events 1	0.00% 0/64	0.00% 0/184

Other adverse events

Measure	Placebo Double Blind Period n=65 participants at risk Placebo taken from day 1 to week 8.	Low Dose Colesevelam Double Blind Period n=65 participants at risk Low dose colesevelam 1.9 grams per day taken from day 1 to week 8.	High Dose Colesevelam Double Blind Period n=64 participants at risk High dose colesevelam 3.8 grams per day taken from day 1 to week 8.	High Dose Colesevelam Open Label Extension n=184 participants at risk All participants of the Open Label Extension (weeks 8-26) took colesevelam 3.8 grams per day.
Infections and infestations nasopharyngitis	4.6% 3/65	6.2% 4/65	6.2% 4/64	5.4% 10/184
Infections and infestations upper respiratory infections NOS	4.6% 3/65	1.5% 1/65	1.6% 1/64	4.9% 9/184
Infections and infestations ear infection NOS	4.6% 3/65	1.5% 1/65	0.00% 0/64	1.6% 3/184
Infections and infestations gastrointestinal viral NOS	3.1% 2/65	0.00% 0/65	0.00% 0/64	2.2% 4/184
Infections and infestations influenza	0.00% 0/65	0.00% 0/65	3.1% 2/64	3.8% 7/184
Gastrointestinal disorders vomiting NOS	1.5% 1/65	3.1% 2/65	1.6% 1/64	0.00% 0/184
Gastrointestinal disorders diarrhea NOS	3.1% 2/65	0.00% 0/65	1.6% 1/64	1.1% 2/184
Gastrointestinal disorders nausea	1.5% 1/65	3.1% 2/65	0.00% 0/64	3.8% 7/184
Respiratory, thoracic and mediastinal disorders rhinitis NOS	0.00% 0/65	4.6% 3/65	0.00% 0/64	1.6% 3/184
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	0.00% 0/65	3.1% 2/65	0.00% 0/64	3.3% 6/184
Nervous system disorders headache	3.1% 2/65	4.6% 3/65	3.1% 2/64	7.6% 14/184
Nervous system disorders dizziness	3.1% 2/65	0.00% 0/65	0.00% 0/64	0.00% 0/184
General disorders fatigue	1.5% 1/65	4.6% 3/65	3.1% 2/64	0.00% 0/184
Investigations blood creatine phosphokinase increased	0.00% 0/65	3.1% 2/65	1.6% 1/64	0.00% 0/184
Musculoskeletal and connective tissue disorders myalgia	0.00% 0/65	3.1% 2/65	0.00% 0/64	0.00% 0/184
Gastrointestinal disorders abdominal pain NOS	0.00% 0/65	0.00% 0/65	0.00% 0/64	3.3% 6/184

Additional Information

Howard Kessler

Daiichi Sankyo

Phone: 732-590-5032

Email: hmkessler@dsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reflects the following restrictive language in the Clinical Study Agreements: "If identified by Daiichi Sankyo,Inc. (DSI), any of DSI's confidential information as defined herein shall be deleted…Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by the Study Site."
• Publication restrictions are in place

Restriction type: OTHER