Trial Outcomes & Findings for An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects (NCT NCT02190747)

NCT ID: NCT02190747

Last Updated: 2021-02-16

Results Overview

A responder was defined as a subject with no or minimal new heterotopic ossification (HO) at flare-up site versus baseline as assessed by plain radiographs at Week 6. Minimal new HO is defined as new HO with an HO score \<=3 in both anterior/posterior (AP) and lateral projections (or if one view is non-interpretable or non-evaluable, then remaining evaluable view is used). The HO score ranges from 0 to 6 where, 0 = no HO and 6 = single contiguous HO with longest dimension \>2 diameters of reference normotopic bone in any projection. The highest HO score from the 2 projections was used. Results from Primary Read reviews are presented. The Primary Read process included a double-read radiology review paradigm with consensus adjudication. Radiography and CT scans were examined independently by scan type, flare-up region, and imaging time point in order to determine whether radiography would be sufficient to measure new HO formation. Only subjects with interpretable outcomes were evaluated.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Baseline (Day 1) and Week 6 (Day 42)
• Results posted on: 2021-02-16

Participant Flow

Eight subjects were randomized 3:1 to either palovarotene or placebo in Cohort 1; 8 additional subjects were randomized 3:1 in an interim period between Cohorts 1 and 2. In Cohort 2, 24 additional fibrodysplasia ossificans progressiva (FOP) subjects were randomized 3:3:2 across 2 weight-based regimens of palovarotene or placebo.

The study included clinically diagnosed FOP subjects at least 6 years of age (Cohort 2) or 15 years of age and older (Cohort 1) with symptomatic onset of a flare-up within 7 days of treatment start and accessible for treatment and follow-up.

Participant milestones

Measure	Palovarotene 10/5 mg Subjects received palovarotene 10 milligram (mg) orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Study STARTED	21	9	10
Overall Study COMPLETED	21	9	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects

Baseline characteristics by cohort

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Total n=40 Participants Total of all reporting groups
Age, Continuous	22.8 years STANDARD_DEVIATION 10.3 • n=5 Participants	17.9 years STANDARD_DEVIATION 8.6 • n=7 Participants	21.2 years STANDARD_DEVIATION 13.7 • n=5 Participants	21.3 years STANDARD_DEVIATION 10.8 • n=4 Participants
Age, Customized Children (2-11 years)	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Age, Customized Adolescents (12-17 years)	5 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Age, Customized Adults (18-64 years)	13 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	22 Participants n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Not available	6 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 6 (Day 42)

Population: The Per Protocol (PP) population included all subjects who were eligible for full analysis set (FAS) population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or computed tomography (CT) at Week 6 sufficient to allow determination of HO at flare-up site.

A responder was defined as a subject with no or minimal new heterotopic ossification (HO) at flare-up site versus baseline as assessed by plain radiographs at Week 6. Minimal new HO is defined as new HO with an HO score <=3 in both anterior/posterior (AP) and lateral projections (or if one view is non-interpretable or non-evaluable, then remaining evaluable view is used). The HO score ranges from 0 to 6 where, 0 = no HO and 6 = single contiguous HO with longest dimension >2 diameters of reference normotopic bone in any projection. The highest HO score from the 2 projections was used. Results from Primary Read reviews are presented. The Primary Read process included a double-read radiology review paradigm with consensus adjudication. Radiography and CT scans were examined independently by scan type, flare-up region, and imaging time point in order to determine whether radiography would be sufficient to measure new HO formation. Only subjects with interpretable outcomes were evaluated.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=9 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Percentage of Responders at Week 6	100 percentage of subjects	88.9 percentage of subjects	88.9 percentage of subjects

SECONDARY outcome

Timeframe: Weeks 6 and 12 (Day 84)

Population: The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.

Low dose CT scan was used as a secondary imaging assessment of HO and was performed at the same time points as plain radiographs. The percentage of subjects with new HO (regardless of the amount of new HO) at the flare-up site as assessed by CT scan and/or plain radiographs at Weeks 6 and 12 were analysed. The results are from Global Read reviews. The holistic Global Read process allowed concurrent review of all modalities across all time points, and provided access to selected clinical data at the time of review.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Percentage of Subjects With New HO at Weeks 6 and 12 Week 6	15.0 percentage of subjects	22.2 percentage of subjects	30.0 percentage of subjects
Percentage of Subjects With New HO at Weeks 6 and 12 Week 12	15.0 percentage of subjects	44.4 percentage of subjects	40.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Weeks 6 and 12

Population: The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.

Interpretation of plain radiographs document the amount (area) of HO on both the AP and lateral radiograph views. The area for each view was a sum of all the new HO at the flare-up location (and thus if there are multiple HO lesions, the area of each lesion was determined and then the total across all lesions were summed to obtain a total new HO). This total new HO sum was used in the analysis of the area of new HO. Results from Primary Read reviews are presented.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Amount (Area) of New HO Formed at the Flare-up Site at Weeks 6 and 12 Week 6	0.00 square millimeters (mm) Standard Deviation 0.000	38.85 square millimeters (mm) Standard Deviation 116.542	75.89 square millimeters (mm) Standard Deviation 176.744
Change From Baseline in Amount (Area) of New HO Formed at the Flare-up Site at Weeks 6 and 12 Week 12	19.00 square millimeters (mm) Standard Deviation 84.955	71.22 square millimeters (mm) Standard Deviation 213.650	621.71 square millimeters (mm) Standard Deviation 1287.519

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The PP population included all subjects who were eligible for FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site. Only subjects with interpretable outcomes were evaluated.

A responder was defined as a subject with no or minimal new HO at the flare-up site versus baseline as assessed by plain radiographs at Week 12. Minimal new HO is defined as new HO with an HO score <=3 in both the AP and lateral projections (or if one view is non-interpretable or non-evaluable, then the remaining evaluable view is used). The HO score ranges from 0 to 6 where, 0 = no HO and 6 = single contiguous HO with longest dimension >2 diameters of the reference normotopic bone in any projection. The highest HO score from the 2 projections was used. Results from the Primary Read reviews are presented. The Primary Read process included a double-read radiology review paradigm with consensus adjudication. Radiography and CT scans were examined independently by scan type, flare-up region, and imaging time point in order to determine whether radiography would be sufficient to measure new HO formation.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=9 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Percentage of Responders at Week 12	95.0 percentage of subjects	88.9 percentage of subjects	77.8 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Bone specific alkaline phosphatase was analysed as a bone and cartilage biomarker.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 Week 2	-1.33 microgram per liter (mcg/L) Standard Deviation 13.267	-3.18 microgram per liter (mcg/L) Standard Deviation 4.619	12.02 microgram per liter (mcg/L) Standard Deviation 35.263
Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 Week 4	-1.41 microgram per liter (mcg/L) Standard Deviation 8.328	3.80 microgram per liter (mcg/L) Standard Deviation 12.072	7.53 microgram per liter (mcg/L) Standard Deviation 10.208
Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 Week 6	-2.53 microgram per liter (mcg/L) Standard Deviation 8.157	0.74 microgram per liter (mcg/L) Standard Deviation 3.316	6.23 microgram per liter (mcg/L) Standard Deviation 6.851
Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 Week 12	2.49 microgram per liter (mcg/L) Standard Deviation 5.506	0.89 microgram per liter (mcg/L) Standard Deviation 6.738	10.00 microgram per liter (mcg/L) Standard Deviation 10.091

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. C-reactive protein was analysed as a inflammation biomarker.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 Week 2	8.62 mg/L Standard Deviation 28.085	0.09 mg/L Standard Deviation 2.370	-1.59 mg/L Standard Deviation 1.909
Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 Week 4	1.48 mg/L Standard Deviation 4.924	23.26 mg/L Standard Deviation 38.311	2.34 mg/L Standard Deviation 3.704
Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 Week 6	0.14 mg/L Standard Deviation 3.419	2.70 mg/L Standard Deviation 7.984	1.20 mg/L Standard Deviation 1.319
Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 Week 12	2.82 mg/L Standard Deviation 11.762	1.27 mg/L Standard Deviation 1.789	-0.30 mg/L Standard Deviation 2.951

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. C-terminal telopeptide was analysed as a bone and cartilage biomarker.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 Week 2	-0.020 mcg/L Standard Deviation 0.290	0.118 mcg/L Standard Deviation 0.359	0.071 mcg/L Standard Deviation 0.342
Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 Week 4	0.015 mcg/L Standard Deviation 0.337	0.095 mcg/L Standard Deviation 0.380	0.188 mcg/L Standard Deviation 0.219
Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 Week 6	0.105 mcg/L Standard Deviation 0.304	0.078 mcg/L Standard Deviation 0.293	0.125 mcg/L Standard Deviation 0.351
Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 Week 12	0.116 mcg/L Standard Deviation 0.241	0.054 mcg/L Standard Deviation 0.285	0.126 mcg/L Standard Deviation 0.197

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Procollagen type 1 N-terminal propeptide was analysed as a bone and cartilage biomarker.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 Week 2	53.022 mcg/L Standard Deviation 72.091	78.930 mcg/L Standard Deviation 113.443	42.058 mcg/L Standard Deviation 77.358
Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 Week 4	123.986 mcg/L Standard Deviation 207.513	117.476 mcg/L Standard Deviation 169.238	194.193 mcg/L Standard Deviation 318.920
Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 Week 6	141.304 mcg/L Standard Deviation 206.163	147.409 mcg/L Standard Deviation 246.219	252.328 mcg/L Standard Deviation 389.359
Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 Week 12	120.489 mcg/L Standard Deviation 211.565	25.766 mcg/L Standard Deviation 233.860	141.367 mcg/L Standard Deviation 213.926

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Procollagen type 1 C-terminal propeptide was analysed as a bone and cartilage biomarker.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 Week 2	22.12 mcg/L Standard Deviation 61.976	23.26 mcg/L Standard Deviation 11.585	82.93 mcg/L Standard Deviation 109.010
Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 Week 4	72.16 mcg/L Standard Deviation 98.697	76.10 mcg/L Standard Deviation 110.041	140.26 mcg/L Standard Deviation 155.036
Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 Week 6	73.36 mcg/L Standard Deviation 130.437	87.19 mcg/L Standard Deviation 96.451	125.31 mcg/L Standard Deviation 110.389
Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 Week 12	51.21 mcg/L Standard Deviation 82.901	47.30 mcg/L Standard Deviation 112.113	96.49 mcg/L Standard Deviation 92.215

SECONDARY outcome

Timeframe: Baseline, Weeks 6 and 12

Population: The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.

Low dose CT scan were used as a secondary imaging assessment of HO, and was performed at the same time points as plain radiographs. Interpretation of the CT scan documented the amount (volume) and grade of HO. The independent reviewer scored HO lesions according to the following scale for HO on CT. Grade 1 = fluid attenuation without evidence of calcification at CT, Grade 2 = calcification of soft tissues without evidence of bone formation, Grade 3 = immature bone formation, and Grade 4 = mature bone with cortical differentiation. Volume of new HO was determined according to the following steps: (1) calculate volume of new HO compared to baseline for each reviewer/HO ID, (2) sum the volume of new HO across HO IDs for each reviewer, and (3) average the volume of new HO across reviewers. Results from Primary Read reviews are presented.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Amount of Bone Formation (Volume) at Weeks 6 and 12 Week 6	2820.53 cubic mm Standard Deviation 11078.233	326.58 cubic mm Standard Deviation 979.733	11459.42 cubic mm Standard Deviation 29759.691
Change From Baseline in Amount of Bone Formation (Volume) at Weeks 6 and 12 Week 12	3857.95 cubic mm Standard Deviation 11860.978	1184.99 cubic mm Standard Deviation 3188.020	16181.64 cubic mm Standard Deviation 41643.976

SECONDARY outcome

Timeframe: Weeks 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

The MRI was utilized to evaluate the presence of soft tissue swelling/edema (and volume of the swelling/edema) and presence of cartilage formation (yes or no). For subjects who could not have an MRI, US was used to assess edema severity for the sub-set of subjects enrolled after this opinion was introduced in a protocol amendment. Imaging film from MRI was assessed by two independent readers. When there was sufficient agreement between the independent readers on volume, both of the independent readings were used for analysis with the volume measurements averaged. When there was insufficient agreement between the independent readers, an adjudication reading was provided and used for analysis. The US was used for soft tissue swelling/edema but not cartilage formation. Percentage calculated as % = 100 x n/N' where N' is the number of subjects with interpretable outcomes. Results from Primary Read reviews are presented.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 Soft tissue swelling: Week 6	50.0 percentage of subjects	50.0 percentage of subjects	66.7 percentage of subjects
Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 Soft tissue swelling: Week 12	60.0 percentage of subjects	66.7 percentage of subjects	66.7 percentage of subjects
Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 Cartilage formation: Week 6	15.4 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 Cartilage formation: Week 12	8.3 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Weeks 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Active range of motion, expressed as the percent of normal arc of motion, measurements at the primary joint associated with the flare-up and adjoining joints was assessed by goniometer.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Percent of Normal Arc of Motion at the Primary Joint (Flare-up Site) at Weeks 6 and 12 Week 6	-0.40 percent of normal arc of motion Standard Deviation 9.574	-1.36 percent of normal arc of motion Standard Deviation 21.336	-0.99 percent of normal arc of motion Standard Deviation 18.951
Change From Baseline in Percent of Normal Arc of Motion at the Primary Joint (Flare-up Site) at Weeks 6 and 12 Week 12	0.58 percent of normal arc of motion Standard Deviation 15.079	-4.23 percent of normal arc of motion Standard Deviation 26.791	-2.31 percent of normal arc of motion Standard Deviation 18.963

SECONDARY outcome

Timeframe: Weeks 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site. Only subjects with non-missing values were presented.

Flare-up movement outcomes were independently assessed by both the subject (or parent of a subject under 8 years of age) and the Investigator at Weeks 6 and 12 by completing the global assessment of movement. The subject/parent completed the global assessment first. Prior to reviewing the subject's assessment, the Investigator completed his/her own assessment of the flare-up outcome. Subjects were assessed how the flare-up affected their movement on a scale ranging 1 to 5 where, 1 = severely worse movement and 5 = better movement compared with study Day 1 (day of first dose of study drug). Investigators were assessed how the flare-up affected the subject's movement on a scale ranging 1 to 5 where, 1 = severely worse movement and 5 = better movement compared with baseline (day of screening physical examination).

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 6 · Score 1	0 Participants	1 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 6 · Score 2	1 Participants	0 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 6 · Score 3	0 Participants	0 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 6 · Score 4	2 Participants	3 Participants	2 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 6 · Score 5	6 Participants	4 Participants	3 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 12 · Score 1	0 Participants	1 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 12 · Score 2	0 Participants	1 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 12 · Score 3	1 Participants	0 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 12 · Score 4	6 Participants	2 Participants	4 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Subject Global Assessment: Week 12 · Score 5	6 Participants	5 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 6 · Score 1	1 Participants	1 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 6 · Score 2	0 Participants	0 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 6 · Score 3	0 Participants	0 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 6 · Score 4	3 Participants	2 Participants	3 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 6 · Score 5	5 Participants	5 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 12 · Score 1	1 Participants	1 Participants	1 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 12 · Score 2	0 Participants	1 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 12 · Score 3	0 Participants	1 Participants	0 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 12 · Score 4	8 Participants	2 Participants	4 Participants
Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 Investigator Global Assessment: Week 12 · Score 5	4 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 9 and 12

Population: The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.

The pain and swelling associated with flare-ups was evaluated using 2 separate numeric rating scales, one for pain and one for swelling. The pain scale ranges from 0 to 10 where, 0 = no pain and 10 = worst pain ever experienced. The swelling scale ranges from 0 to 10 where, 0 = no swelling and 10 = worst swelling ever experienced. The Faces Pain Scale - Revised (FPS-R) was used for children less than 8 years old. The FPS-R ranges from 0 to 10 where, 0 = no pain and 10 = very much pain in two-point increments.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up pain: Week 2	-2.5 units on a scale Standard Deviation 2.50	0.0 units on a scale Standard Deviation 2.40	-2.0 units on a scale Standard Deviation 1.76
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up pain: Week 4	-3.2 units on a scale Standard Deviation 2.46	-1.3 units on a scale Standard Deviation 1.58	-1.9 units on a scale Standard Deviation 3.14
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up pain: Week 6	-3.5 units on a scale Standard Deviation 2.78	-1.3 units on a scale Standard Deviation 1.58	-2.4 units on a scale Standard Deviation 2.91
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up pain: Week 9	-3.8 units on a scale Standard Deviation 2.62	-1.1 units on a scale Standard Deviation 1.64	-2.1 units on a scale Standard Deviation 1.85
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up pain: Week 12	-3.6 units on a scale Standard Deviation 2.72	-1.9 units on a scale Standard Deviation 2.42	-2.2 units on a scale Standard Deviation 2.53
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up swelling: Week 2	-1.4 units on a scale Standard Deviation 2.76	-1.3 units on a scale Standard Deviation 2.93	-2.3 units on a scale Standard Deviation 2.79
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up swelling: Week 4	-1.7 units on a scale Standard Deviation 3.30	-1.9 units on a scale Standard Deviation 1.81	-2.0 units on a scale Standard Deviation 3.30
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up swelling: Week 6	-2.2 units on a scale Standard Deviation 3.32	-2.0 units on a scale Standard Deviation 2.45	-2.6 units on a scale Standard Deviation 3.50
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up swelling: Week 9	-2.7 units on a scale Standard Deviation 3.32	-2.3 units on a scale Standard Deviation 2.43	-1.9 units on a scale Standard Deviation 4.41
Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 Flare-up swelling: Week 12	-2.1 units on a scale Standard Deviation 3.73	-2.5 units on a scale Standard Deviation 2.20	-2.3 units on a scale Standard Deviation 3.16

SECONDARY outcome

Timeframe: Weeks 6 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

Subjects were given a list of FOP assistive devices and adaptations and asked to select those they use for daily living. The FOP assistive devices and adaptations included mobility aids, care attendants, eating tools, personal care tools/aids, bathroom aids and devices, bedroom aids and devices, home adaptations, work environment adaptations, technology adaptations, sports and recreation adaptations, school, and medical therapies for daily living.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Percentage of Subjects Who Used Any Assistive Devices and Adaptations for Daily Living at Weeks 6 and 12 Week 6	85.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects
Percentage of Subjects Who Used Any Assistive Devices and Adaptations for Daily Living at Weeks 6 and 12 Week 12	90.5 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects

SECONDARY outcome

Timeframe: From Day 1 to Day 84

Population: The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.

The duration of active symptomatic flare-up was defined as the number of days the subject reported the presence of symptoms in the diary ('Is your flare-up ongoing today?') from Day 1 to study completion at Day 84. The mean number of days of active, symptomatic flare-up is presented for subjects with evaluable diary data.

Outcome measures

Measure	Palovarotene 10/5 mg n=17 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=8 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Duration of Active Symptomatic Flare-up	22.1 days Standard Deviation 20.53	44.1 days Standard Deviation 38.36	34.4 days Standard Deviation 34.15

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 9 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

The FOP-PFQ consists of 28 questions rated on scales from 1 to 5, with lower scores denoting more difficulty. The adult form of the FOP-PFQ was administered to subjects 15 years of age and older. There are two Pediatric FOP-PFQ (FOP-PFQ-P) forms: a self-completed form for 8 to 14 year-olds and a parent proxy-completed form for 5 to 14 year-olds. For subjects between 8 to 14 years of age, both the self-completed (for 8 to 14 year-olds) and the proxy-completed (for 5 to 14 year olds) forms of the FOP-PFQ-P were administered. However, only the proxy-completed form was used for analysis. Percentage of worst scores ranges from 0% to 100% with 0% = best possible function and 100% = worst possible function. Change from baseline for each time point is presented.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 Week 2	0.95 units on a scale Standard Deviation 5.484	0.31 units on a scale Standard Deviation 3.818	2.11 units on a scale Standard Deviation 6.659
Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 Week 4	3.42 units on a scale Standard Deviation 7.932	2.67 units on a scale Standard Deviation 7.200	2.91 units on a scale Standard Deviation 8.427
Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 Week 6	3.79 units on a scale Standard Deviation 7.787	2.88 units on a scale Standard Deviation 7.550	1.75 units on a scale Standard Deviation 5.980
Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 Week 9	1.89 units on a scale Standard Deviation 5.432	-0.52 units on a scale Standard Deviation 7.881	4.91 units on a scale Standard Deviation 13.185
Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 Week 12	4.22 units on a scale Standard Deviation 7.915	1.08 units on a scale Standard Deviation 8.724	3.02 units on a scale Standard Deviation 9.587

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 9 and 12

Population: The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.

The PROMIS Global Health contains 10 questions which are rated on scales from 1 to 5 or 0 to 10. Global physical health scores were calculated as the sum of scores from parameters 3, 6, 7, and 8 and ranges from 4 to 20 where, 4 = worse health and 20 = better health. Global mental health scores were calculated as the sum of scores from parameters 2, 4, 5, and 10 and ranges from 4 to 20 where, 4 = worse health and 20 = better health. For paediatric subjects, the PROMIS was administered as per the adult version. However, there is a single total score for the paediatric PROMIS (as opposed to global physical and global mental health scores as are in the adult version). The total score were converted to a T-score. A T-score of 50 is normal and increments of 10 are +/- 1 standard deviation away from the norm. A T-score <50 indicates worse health, while a T-score >50 indicates better health. The higher values (positive changes) indicate better health.

Outcome measures

Measure	Palovarotene 10/5 mg n=21 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 Participants Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Physical Health T-Score: Week 2	2.76 t-score Standard Deviation 5.308	0.00 t-score Standard Deviation 1.768	5.90 t-score Standard Deviation 2.087
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Physical Health T-Score: Week 4	4.66 t-score Standard Deviation 6.590	2.66 t-score Standard Deviation 4.345	5.56 t-score Standard Deviation 2.904
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Physical Health T-Score: Week 6	4.69 t-score Standard Deviation 5.585	7.08 t-score Standard Deviation 6.591	5.73 t-score Standard Deviation 2.750
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Physical Health T-Score: Week 9	4.96 t-score Standard Deviation 5.489	5.58 t-score Standard Deviation 3.381	4.94 t-score Standard Deviation 3.135
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only:Global Physical Health T-Score: Week 12	3.97 t-score Standard Deviation 6.764	4.98 t-score Standard Deviation 6.246	3.78 t-score Standard Deviation 3.883
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Mental Health T-Score: Week 2	3.66 t-score Standard Deviation 5.216	3.20 t-score Standard Deviation 2.024	1.98 t-score Standard Deviation 3.124
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Mental Health T-Score: Week 4	3.32 t-score Standard Deviation 5.066	2.28 t-score Standard Deviation 2.700	7.30 t-score Standard Deviation 5.609
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Mental Health T-Score: Week 6	4.15 t-score Standard Deviation 6.878	2.54 t-score Standard Deviation 4.980	4.34 t-score Standard Deviation 5.850
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Mental Health T-Score: Week 9	4.62 t-score Standard Deviation 7.684	1.68 t-score Standard Deviation 3.641	5.38 t-score Standard Deviation 5.438
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Adult-only: Global Mental Health T-Score: Week 12	4.33 t-score Standard Deviation 7.527	3.10 t-score Standard Deviation 4.127	1.04 t-score Standard Deviation 3.664
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Paediatric-only: Global Health T-Score: Week 2	-2.27 t-score Standard Deviation 4.278	1.05 t-score Standard Deviation 2.352	-1.80 t-score Standard Deviation 4.668
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Paediatric-only: Global Health T-Score: Week 4	-0.57 t-score Standard Deviation 2.499	1.43 t-score Standard Deviation 6.352	-6.40 t-score Standard Deviation 4.314
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Paediatric-only: Global Health T-Score: Week 6	-2.23 t-score Standard Deviation 3.499	2.80 t-score Standard Deviation 4.955	-3.30 t-score Standard Deviation 7.826
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Paediatric-only: Global Health T-Score: Week 9	1.17 t-score Standard Deviation 2.021	1.83 t-score Standard Deviation 1.434	-3.50 t-score Standard Deviation 4.668
Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 Paediatric-only: Global Health T-Score: Week 12	0.17 t-score Standard Deviation 7.572	-2.13 t-score Standard Deviation 2.964	-6.57 t-score Standard Deviation 1.950

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hours (hrs) post-dose at Week 2, and at Week 4 or 6

Population: The Pharmacokinetic (PK) population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The Cmax of palovarotene was determined.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Maximum Measured Plasma Concentration (Cmax) of Palovarotene Week 2	95620.00 picograms per milliliter (pg/mL) Standard Deviation 30296.77	35620.00 picograms per milliliter (pg/mL) Standard Deviation 19882.08	—
Maximum Measured Plasma Concentration (Cmax) of Palovarotene Week 4/Week 6	45505.88 picograms per milliliter (pg/mL) Standard Deviation 17061.05	18958.57 picograms per milliliter (pg/mL) Standard Deviation 9238.62	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6

Population: The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The Cmin of palovarotene was determined.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Minimum Measured Plasma Concentration (Cmin) of Palovarotene Week 2	3128.53 pg/mL Standard Deviation 2358.88	1739.40 pg/mL Standard Deviation 963.68	—
Minimum Measured Plasma Concentration (Cmin) of Palovarotene Week 4/Week 6	3879.00 pg/mL Standard Deviation 7042.29	614.14 pg/mL Standard Deviation 289.72	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6

Population: The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The Tmax obtained by inspection of palovarotene was determined.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Time of Maximum Measured Plasma Concentration (Tmax) of Palovarotene Week 2	3.00 hr Interval 2.83 to 6.03	2.77 hr Interval 2.08 to 5.88	—
Time of Maximum Measured Plasma Concentration (Tmax) of Palovarotene Week 4/Week 6	3.00 hr Interval 2.75 to 6.0	3.00 hr Interval 3.0 to 6.0	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6

Population: The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The t1/2 was calculated as ln(2)/ λz. The number of data points included in the regression was determined by visual inspection, but a minimum of three data points in the terminal phase, excluding Cmax, was required to estimate λz.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Apparent Terminal Elimination Half-life (t1/2) of Palovarotene Week 2	4.33 hr Interval 3.3 to 6.51	5.18 hr Interval 3.29 to 5.94	—
Apparent Terminal Elimination Half-life (t1/2) of Palovarotene Week 4/Week 6	4.39 hr Interval 3.11 to 6.38	4.40 hr Interval 4.13 to 5.11	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6

Population: The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The AUC(0-24hr) was calculated using linear trapezoid rule.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Area Under the Plasma Concentration Versus Time Curve Over the 24-hr Dosing Interval (AUC[0-24hr]) of Palovarotene Week 2	686308.92 hr*pg/mL Standard Deviation 246797.81	350124.65 hr*pg/mL Standard Deviation 181967.49	—
Area Under the Plasma Concentration Versus Time Curve Over the 24-hr Dosing Interval (AUC[0-24hr]) of Palovarotene Week 4/Week 6	311082.39 hr*pg/mL Standard Deviation 128622.73	142748.47 hr*pg/mL Standard Deviation 84838.75	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6

Population: The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.

The CL/F was defined as dose/AUC0-24hr.

Outcome measures

Measure	Palovarotene 10/5 mg n=20 Participants Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=8 Participants Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Apparent Clearance of Palovarotene (CL/F) Week 2	15.55 L/hr Standard Deviation 7.03	12.84 L/hr Standard Deviation 4.07	—
Apparent Clearance of Palovarotene (CL/F) Week 4/Week 6	17.71 L/hr Standard Deviation 7.44	19.51 L/hr Standard Deviation 10.66	—

Adverse Events

Palovarotene 10/5 mg

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Palovarotene 5/2.5 mg

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Palovarotene 10/5 mg n=21 participants at risk Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 participants at risk Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 participants at risk Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
General disorders Condition aggravated	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Nervous system disorders Myoclonus	4.8% 1/21 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).

Other adverse events

Measure	Palovarotene 10/5 mg n=21 participants at risk Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.	Palovarotene 5/2.5 mg n=9 participants at risk Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.	Placebo n=10 participants at risk Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Injury, poisoning and procedural complications Post-traumatic pain	9.5% 2/21 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Injury, poisoning and procedural complications Fall	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Haemoglobin decreased	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Lipase increased	9.5% 2/21 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Blood alkaline phosphatase increased	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Blood bilirubin increased	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Blood thyroid stimulating hormone decreased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Gamma-glutamyltransferase increased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Amylase increased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Blood potassium increased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Vascular disorders Pallor	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Condition aggravated	61.9% 13/21 • Number of events 27 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	30.0% 3/10 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Pyrexia	4.8% 1/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	33.3% 3/9 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Application site erythema	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Fatigue	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Feeling cold	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Vessel puncture site bruise	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
General disorders Chest pain	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Psychiatric disorders Insomnia	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Psychiatric disorders Irritability	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Injury, poisoning and procedural complications Contusion	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Injury, poisoning and procedural complications Excoriation	9.5% 2/21 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Thyroxine free increased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Investigations Thyroxine increased	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Respiratory, thoracic and mediastinal disorders Cough	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Nervous system disorders Headache	38.1% 8/21 • Number of events 9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	30.0% 3/10 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Nervous system disorders Dizziness	4.8% 1/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Nervous system disorders Hypoaesthesia	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Nervous system disorders Migraine	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Eye disorders Dry eye	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Eye disorders Eye pruritus	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Eye disorders Vision blurred	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Lip dry	33.3% 7/21 • Number of events 8 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	55.6% 5/9 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Nausea	28.6% 6/21 • Number of events 7 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Chapped lips	23.8% 5/21 • Number of events 6 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Diarrhoea	19.0% 4/21 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Dry mouth	14.3% 3/21 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Abdominal pain	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Vomiting	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Constipation	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Flatulence	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Frequent bowel movements	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Renal and urinary disorders Pollakiuria	9.5% 2/21 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Renal and urinary disorders Haematuria	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Renal and urinary disorders Polyuria	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Renal and urinary disorders Glycosuria	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Dry skin	81.0% 17/21 • Number of events 38 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	55.6% 5/9 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	30.0% 3/10 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Erythema	14.3% 3/21 • Number of events 6 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Pruritus generalised	19.0% 4/21 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Dermatitis acneiform	19.0% 4/21 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Pruritus	19.0% 4/21 • Number of events 5 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Eczema	9.5% 2/21 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Rash maculo-papular	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Skin exfoliation	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Dandruff	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Rash	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Macule	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Arthralgia	47.6% 10/21 • Number of events 13 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	60.0% 6/10 • Number of events 14 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	33.3% 3/9 • Number of events 4 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Joint swelling	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Joint stiffness	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Neck pain	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Back pain	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	20.0% 2/10 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Musculoskeletal and connective tissue disorders Muscle spasms	4.8% 1/21 • Number of events 3 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Metabolism and nutrition disorders Hypercholesterolaemia	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Metabolism and nutrition disorders Increased appetite	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Upper respiratory tract infection	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	22.2% 2/9 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Influenza	9.5% 2/21 • Number of events 2 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Pharyngitis	4.8% 1/21 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Nasopharyngitis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	11.1% 1/9 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/10 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Oral candidiasis	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Infections and infestations Urinary tract infection	0.00% 0/21 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	0.00% 0/9 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).	10.0% 1/10 • Number of events 1 • From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days. Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).

Additional Information

Medical Director

Ipsen

Phone: see email

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place