Trial Outcomes & Findings for Study Evaluating Two Dose Levels of Targretin Capsules in Participants With Refractory Cutaneous T-Cell Lymphoma (CTCL) (NCT NCT01007448)

NCT ID: NCT01007448

Last Updated: 2019-11-12

Results Overview

Index lesion symptoms/grade include: erythema=0 (no evidence)-8 (very severe); scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence of change)-8 (very severe change); area of involvement=0 (0 centimeters \[cm\]\^2)-18 (\>300 cm\^2). CA generated by sum of grades of signs/symptoms for each index lesion. Index lesion CA grade at baseline was divided into CA grade at each subsequent study visit to determine participant's response to treatment. Ratio of CA \<1.0=improvement in disease; ratio \>1.0=worsening of disease. Tumor response as determined by CA=percentage of participants achieving CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of histologic signs of CTCL); CCR (CA ratio=0 and no clinically abnormal lymph nodes); and PR (CA ratio=≤0.5, \<25% increase in number/aggregate area of abnormal lymph nodes/tumors, and no new abnormal lymph nodes in documented area of absence of disease).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 59 participants
• Primary outcome timeframe: Baseline up to Week 24
• Results posted on: 2019-11-12

Participant Flow

Participants were randomized in a 1:1 ratio to bexarotene 150 milligrams (mg)/square meter (m^2)/day or 300 mg/m^2/day.

Participant milestones

Measure	Bexarotene 150 mg/m^2/Day Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Overall Study STARTED	30	29
Overall Study Full Analysis Population	30	29
Overall Study Safety Population	30	29
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	10	9

Reasons for withdrawal

Measure	Bexarotene 150 mg/m^2/Day Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Overall Study Continuing Prohibited Systemic Drugs	1	0
Overall Study Staph Skin Infection Flare	1	0
Overall Study Participant Leaving the Country	1	0
Overall Study Participant Given Prohibited Medication	1	0
Overall Study Progressive Disease	1	2
Overall Study Lack of Efficacy	2	0
Overall Study Withdrawal by Subject	2	3
Overall Study Adverse Event	1	4

Baseline Characteristics

Study Evaluating Two Dose Levels of Targretin Capsules in Participants With Refractory Cutaneous T-Cell Lymphoma (CTCL)

Baseline characteristics by cohort

Measure	Bexarotene 150 mg/m^2/Day n=30 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.	Total n=59 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 14.80 • n=93 Participants	61.0 years STANDARD_DEVIATION 13.94 • n=4 Participants	60.6 years STANDARD_DEVIATION 14.26 • n=27 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	13 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	16 Participants n=4 Participants	33 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population).

Index lesion symptoms/grade include: erythema=0 (no evidence)-8 (very severe); scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence of change)-8 (very severe change); area of involvement=0 (0 centimeters [cm]^2)-18 (>300 cm^2). CA generated by sum of grades of signs/symptoms for each index lesion. Index lesion CA grade at baseline was divided into CA grade at each subsequent study visit to determine participant's response to treatment. Ratio of CA <1.0=improvement in disease; ratio >1.0=worsening of disease. Tumor response as determined by CA=percentage of participants achieving CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of histologic signs of CTCL); CCR (CA ratio=0 and no clinically abnormal lymph nodes); and PR (CA ratio=≤0.5, <25% increase in number/aggregate area of abnormal lymph nodes/tumors, and no new abnormal lymph nodes in documented area of absence of disease).

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=30 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Number of Participants With Tumor Response (Complete Response [CR], Clinical Complete Response [CCR], and Partial Response [PR]) in up to 5 Index Lesions as Determined by Investigator's Composite Assessment (CA) of Index Lesion Disease Severity CR	0 Participants	0 Participants
Number of Participants With Tumor Response (Complete Response [CR], Clinical Complete Response [CCR], and Partial Response [PR]) in up to 5 Index Lesions as Determined by Investigator's Composite Assessment (CA) of Index Lesion Disease Severity CCR	2 Participants	3 Participants
Number of Participants With Tumor Response (Complete Response [CR], Clinical Complete Response [CCR], and Partial Response [PR]) in up to 5 Index Lesions as Determined by Investigator's Composite Assessment (CA) of Index Lesion Disease Severity PR	5 Participants	7 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population).

The PGA was an assessment of the overall extent of improvement/worsening from Baseline of the participant's overall disease compared with the condition every 4 weeks thereafter during treatment. CR=PGA grade of 0 (completely clear of disease since Baseline) and absence of histologic signs of CTCL. CCR=PGA grade of 0. PR=PGA grade of 1 (almost clear [≥90%-<100%] of disease since Baseline), 2 (marked improvement [≥75%-<90%] of disease since Baseline), 3 (moderate improvement [≥50%-<70%] of disease since Baseline). Stable Disease (SD)=PGA grade of 4 (slight improvement [<25%-<50%] of disease since Baseline) or 5 (no change in disease [+/-<25% change since Baseline]). Progressive Disease (PD)=PGA grade of 6 (worse disease [≥25%] than at baseline). If visceral disease or an abnormal lymph node was located in a documented area of absence of disease, then PD would be reported for the participant.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=30 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition CR	0 Participants	0 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition CCR	1 Participants	3 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition PR	5 Participants	8 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition SD	23 Participants	16 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition PD	0 Participants	0 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition Unknown	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population).

To determine BSA involvement, the area of the participant's palm was defined as 1% of the participant's BSA. The extent of involvement of disease was determined as multiples of the participant's palm area and expressed as a percentage of the participant's total BSA at Baseline (Day 1) and every 4 weeks thereafter during treatment. CR=percent BSA 0% and documented absence of histologic signs of CTCL. CCR=Percent BSA 0%. PR=a decrease from Baseline in percent BSA of at least 50%. SD=none of the response classifications (that is, CR, CCR, PR, or PD) accurately describe the disease status. PD=an increase from Baseline in percent BSA of at least 25%.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=30 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement CR	1 Participants	2 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement CCR	0 Participants	1 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement PR	6 Participants	7 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement SD	22 Participants	17 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement PD	0 Participants	0 Participants
Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement Unknown	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for CA of index lesion disease severity.

Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, absence of CTCL histologic signs); CCR (CA ratio=0; no clinically abnormal lymph nodes); PR (CA ratio=≤0.5, <25% increase in number/aggregate area of abnormal lymph nodes/tumors, no new abnormal lymph nodes in documented area of absence of disease).

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=7 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=10 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Duration of Tumor Response (CR, CCR, or PR) as Determined by Investigator's CA of Index Lesion Disease Severity	65.9 days Standard Deviation 41.86	83.7 days Standard Deviation 36.50

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for PGA of clinical condition.

Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. PGA was an assessment of the overall extent of improvement/worsening from Baseline of the participant's overall disease compared with the condition every 4 weeks thereafter during treatment. CR=PGA grade of 0 (completely clear of disease since Baseline) and absence of histologic signs of CTCL. CCR=PGA grade of 0. PR=PGA grade of 1 (almost clear [≥90%-<100%] of disease since Baseline), 2 (marked improvement [≥75%-<90%] of disease since Baseline), 3 (moderate improvement [≥50%-<70%] of disease since Baseline).

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=6 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=11 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Duration of Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition	111.5 days Standard Deviation 34.61	69.4 days Standard Deviation 38.93

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for percent of BSA involvement.

Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. To determine BSA, the area of the participant's palm was defined as 1% of the participant's BSA. The extent of involvement of disease was determined as multiples of the participant's palm area and expressed as a percentage of the participant's total BSA at Baseline (Day 1) and every 4 weeks thereafter during treatment. CR=percent BSA 0% and documented absence of histologic signs of CTCL. CCR=Percent BSA 0%. PR=a decrease from Baseline in percent BSA of at least 50%.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=7 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=10 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Duration of Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement	99.4 days Standard Deviation 41.69	54.1 days Standard Deviation 42.18

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for CA of index lesion disease severity.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of CTCL histologic signs); CCR (CA ratio=0 and no clinically abnormal lymph nodes); and PR (CA ratio=≤0.5, <25% increase in number/aggregate area of abnormal lymph nodes/tumors, and no new abnormal lymph nodes in documented area of absence of disease).

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=7 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=10 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Response (CR, CCR, or PR) as Determined by CA of Index Lesion Disease Severity	99.9 days Standard Deviation 39.14	91.6 days Standard Deviation 37.20

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for PGA of clinical condition.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. PGA was an assessment of the overall extent of improvement/worsening from Baseline of the participant's overall disease compared with the condition every 4 weeks thereafter during treatment. CR=PGA grade of 0 (completely clear of disease since Baseline) and absence of histologic signs of CTCL. CCR=PGA grade of 0. PR=PGA grade of 1 (almost clear [≥90%-<100%] of disease since Baseline), 2 (marked improvement [≥75%-<90%] of disease since Baseline), 3 (moderate improvement [≥50%-<70%] of disease since Baseline).

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=6 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=11 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition	53.5 days Standard Deviation 23.32	103.5 days Standard Deviation 41.34

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for percent of BSA involvement.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. To determine BSA, the area of the participant's palm was defined as 1% of the participant's BSA. The extent of involvement of disease was determined as multiples of the participant's palm area and expressed as a percentage of the participant's total BSA at Baseline (Day 1) and every 4 weeks thereafter during treatment. CR=percent BSA 0% and documented absence of histologic signs of CTCL. CCR=Percent BSA 0%. PR=a decrease from Baseline in percent BSA of at least 50%.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=7 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=10 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement	66.1 days Standard Deviation 36.97	117.0 days Standard Deviation 41.90

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with evaluable PD data for CA of index lesion disease severity.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Criteria for PD requires at least 1 component of the following: CA ratio=≥1.25, ≥25% increase in number/aggregate area of abnormal lymph nodes/tumors, or no new abnormal lymph nodes in documented area of absence of disease.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=1 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=2 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Progression as Determined by CA of Index Lesion Disease Severity	203.0 days Standard Deviation NA NA=Not available. Standard deviation cannot be calculated with an N of 1.	77.5 days Standard Deviation 58.69

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with progression.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. PGA was an assessment of the overall extent of improvement/worsening from Baseline of the participant's overall disease compared with the condition every 4 weeks thereafter during treatment. PD=PGA grade of 6 (worse disease [≥25%] than at baseline). If visceral disease or an abnormal lymph node was located in a documented area of absence of disease, then PD would be reported for the participant.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=2 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Progression as Determined by PGA of Clinical Condition	—	115.5 days Standard Deviation 4.95

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Participants who received at least 1 dose of study drug (Full Analysis Population) and with progression.

Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. To determine BSA involvement, the area of the participant's palm was defined as 1% of the participant's BSA. The extent of involvement of disease was determined as multiples of the participant's palm area and expressed as a percentage of the participant's total BSA at Baseline (Day 1) and every 4 weeks thereafter during treatment. PD=an increase from Baseline in percent BSA of at least 25%.

Outcome measures

Measure	Bexarotene 150 mg/m^2/Day n=2 Participants Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=2 Participants Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Time to Tumor Progression as Determined by Percent BSA Involvement	86.0 days Standard Deviation 1.41	88.0 days Standard Deviation 43.84

Adverse Events

Bexarotene 150 mg/m^2/Day

Serious events: 11 serious events

Other events: 21 other events

Deaths: 0 deaths

Bexarotene 300 mg/m^2/Day

Serious events: 13 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bexarotene 150 mg/m^2/Day n=30 participants at risk Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 participants at risk Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Blood and lymphatic system disorders Bone marrow failure	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	10.3% 3/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Blood and lymphatic system disorders Neutropenia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	10.3% 3/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Blood triglycerides increased	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Metabolism and nutrition disorders Hypertriglyceridaemia	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	31.0% 9/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Renal and urinary disorders Renal failure	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Blood and lymphatic system disorders Anaemia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Cardiac disorders Cardiac failure congestive	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Endocrine disorders Hypothyroidism	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Nervous system disorders Syncope	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Cardiac disorders Atrioventricular block first degree	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
General disorders Chest pain	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
General disorders Oedema peripheral	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Hepatobiliary disorders Cholecystitis	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Pneumonia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Injury, poisoning and procedural complications Lumbar vertebral fracture	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mycosis fungoides	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Renal and urinary disorders Hydronephrosis	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Vascular disorders Peripheral vascular disorder	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).

Other adverse events

Measure	Bexarotene 150 mg/m^2/Day n=30 participants at risk Participants received bexarotene 150 mg/m\^2/day once daily for 24 weeks.	Bexarotene 300 mg/m^2/Day n=29 participants at risk Participants received bexarotene 300 mg/m\^2/day once daily for 24 weeks.
Metabolism and nutrition disorders Hypertriglyceridemia	56.7% 17/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	48.3% 14/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Endocrine disorders Hypothyroidism	40.0% 12/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	51.7% 15/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Nervous system disorders Headache	23.3% 7/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	31.0% 9/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Metabolism and nutrition disorders Hypercholesterolemia	23.3% 7/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	24.1% 7/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Skin and subcutaneous tissue disorders Skin exfoliation	16.7% 5/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	17.2% 5/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Blood and lymphatic system disorders Neutropenia	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	17.2% 5/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Blood triglycerides increased	10.0% 3/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	13.8% 4/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Thyroxine free decreased	13.3% 4/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	13.8% 4/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Alanine aminotransferase increased	10.0% 3/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	13.8% 4/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Blood and lymphatic system disorders Bone marrow failure	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	10.3% 3/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
General disorders Oedema peripheral	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	13.8% 4/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	10.3% 3/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Bacterial test positive	13.3% 4/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Gastrointestinal disorders Diarrhea	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	10.3% 3/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
General disorders Fatigue	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Urinary tract infection	10.0% 3/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations White blood cell count decreased	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Vascular disorders Hypertension	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Muscle spasms	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Gastrointestinal disorders Nausea	3.3% 1/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Neutrophil count decreased	10.0% 3/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Sinusitis	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Upper respiratory tract infection	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	3.4% 1/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Gastrointestinal disorders Constipation	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Metabolism and nutrition disorders Dehydration	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Hypercreatinaemia	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Psychiatric disorders Insomnia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Nervous system disorders Lethargy	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Nasopharyngitis	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Osteoporosis	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Infections and infestations Pnemonia	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Renal and urinary disorders Pollakiuria	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Renal and urinary disorders Proteinuria	6.7% 2/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	0.00% 0/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	6.9% 2/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Investigations Aspartate aminotransferase increased	10.0% 3/30 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).	13.8% 4/29 • Baseline up to Week 28 Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).

Additional Information

Director of Clinical Operations

Bausch Health Americas, Inc.

Email: aloncaric@bauschhealth.com

Results disclosure agreements

• Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
• Publication restrictions are in place

Restriction type: OTHER