Trial Outcomes & Findings for An Efficacy and Safety Study of Palovarotene for the Treatment of MO (NCT NCT03442985)
NCT ID: NCT03442985
Last Updated: 2022-08-01
Results Overview
The annualized rate of new OCs was assessed by whole-body magnetic resonance imaging (MRI) (that is, the total number of new OCs divided by the time in years between the baseline and latest post-baseline MRI).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
193 participants
Primary outcome timeframe
Month 12
Results posted on
2022-08-01
Participant Flow
This Phase 2 placebo-controlled study was conducted in pediatric participants with multiple osteochondromas (MO) at 29 study sites in 11 countries between 22 March 2018 and 30 October 2020. For sites in the European Union, participants from 7 to \<15 years of age were enrolled first and participants from 2 to \<7 years of age were enrolled after the 6-month bone safety data from at least 20 skeletally immature participants.
Study consisted of a screening period (up to 35 days), followed by a double-blind treatment period (24 months) and safety follow-up period (6 months). Participants were randomized in a 1:1:1 ratio to palovarotene 2.5 milligram (mg) or 5.0 mg or placebo. A total of 193 participants received at least 1 dose of study drug and were included in the study analysis.
Participant milestones
| Measure |
Placebo
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Overall Study
STARTED
|
62
|
66
|
65
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
62
|
66
|
65
|
Reasons for withdrawal
| Measure |
Placebo
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Overall Study
Sponsor Request
|
55
|
60
|
54
|
|
Overall Study
Lost to Follow-up
|
5
|
2
|
7
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
4
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
An Efficacy and Safety Study of Palovarotene for the Treatment of MO
Baseline characteristics by cohort
| Measure |
Placebo
n=62 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=66 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=65 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
Total
n=193 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
7.9 years
STANDARD_DEVIATION 2.5 • n=93 Participants
|
7.8 years
STANDARD_DEVIATION 3.1 • n=4 Participants
|
7.4 years
STANDARD_DEVIATION 3.1 • n=27 Participants
|
7.7 years
STANDARD_DEVIATION 2.9 • n=483 Participants
|
|
Age, Customized
2 to 5 years
|
13 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
49 Participants
n=483 Participants
|
|
Age, Customized
6 to 10 years
|
38 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
35 Participants
n=27 Participants
|
106 Participants
n=483 Participants
|
|
Age, Customized
11 to 14 years
|
11 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
38 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
76 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=93 Participants
|
40 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
117 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
48 Participants
n=93 Participants
|
50 Participants
n=4 Participants
|
52 Participants
n=27 Participants
|
150 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black Or African American
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
American Indian Or Alaska Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Missing
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
20 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
56 Participants
n=93 Participants
|
58 Participants
n=4 Participants
|
57 Participants
n=27 Participants
|
171 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Month 12Population: The Full Analysis Set (FAS) included randomized participants who received at least 1 dose of study drug. Only data from the 56 participants for whom Month 12 efficacy imaging data were available were included in the analysis.
The annualized rate of new OCs was assessed by whole-body magnetic resonance imaging (MRI) (that is, the total number of new OCs divided by the time in years between the baseline and latest post-baseline MRI).
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=17 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=23 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Annualized Rate of New Osteochondromas (OCs)
|
0.119 number of new OCs per year
Interval 0.031 to 0.461
|
0.363 number of new OCs per year
Interval 0.148 to 0.888
|
0.172 number of new OCs per year
Interval 0.073 to 0.404
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Month 12Population: The FAS included randomized participants who received at least 1 dose of study drug. Only data from the 56 participants for whom Month 12 efficacy imaging data were available were included in the analysis.
The change from baseline in the total volume of OCs was assessed by whole-body MRI. Baseline was defined as the last available value prior to first administration of study drug.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=17 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=23 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Mean Change From Baseline in the Total Volume of New OCs at Month 12
|
10476.7 cubic millimeter
Standard Deviation 23294.9
|
5250.5 cubic millimeter
Standard Deviation 11754.7
|
10911.0 cubic millimeter
Standard Deviation 35869.6
|
SECONDARY outcome
Timeframe: Month 12Population: The FAS included randomized participants who received at least 1 dose of study drug. Only data from the 56 participants for whom Month 12 efficacy imaging data were available were included in the analysis.
The percentage of participants with no new OCs as assessed by whole-body MRI. Participants with new OCs not identified by MRI due to surgical resection during the treatment period were categorized as having new OCs for this analysis.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=17 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=23 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Percentage of Participants With No New OCs
|
62.5 percentage of participants
|
47.1 percentage of participants
|
56.5 percentage of participants
|
SECONDARY outcome
Timeframe: Month 12Population: The FAS included randomized participants who received at least 1 dose of study drug. Only data from the 56 participants for whom Month 12 efficacy imaging data were available were included in the analysis.
The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=18 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=22 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Annualized Rate of New or Worsening Deformities
|
1.797 number of deformities per year
Interval 1.272 to 2.537
|
1.802 number of deformities per year
Interval 1.209 to 2.684
|
1.895 number of deformities per year
Interval 1.584 to 2.266
|
SECONDARY outcome
Timeframe: Month 12Population: The FAS included randomized participants who received at least 1 dose of study drug. Participants with planned surgeries within 6 months of enrollment to remove symptomatic OCs or to correct deformities present at baseline, and/or had surgical procedures that were a continuation of a previous procedure were excluded in the analysis.
The MO-related surgeries included any procedure indicated for the treatment of MO, such as an excision of a symptomatic OC or correction of a limb deformity.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=8 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=7 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Annualized Rate of MO-Related Surgeries
|
2.087 number of MO-related surgeries per year
Interval 1.099 to 3.964
|
3.454 number of MO-related surgeries per year
Interval 1.85 to 6.451
|
2.231 number of MO-related surgeries per year
Interval 1.638 to 3.038
|
SECONDARY outcome
Timeframe: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dosePopulation: The Pharmacokinetic Set (PKS) included participants receiving treatment with palovarotene and with evaluable PK data.
The Cmax,ss of palovarotene was evaluated. The pharmacokinetic (PK) sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Outcome measures
| Measure |
Placebo
n=49 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=52 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Maximum Observed Plasma Drug Concentrations at Steady State (Cmax,ss) of Palovarotene
|
18.0 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 50.2
|
34.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 63.3
|
—
|
SECONDARY outcome
Timeframe: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dosePopulation: The PKS included participants receiving treatment with palovarotene and with evaluable PK data.
The Cmin,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Outcome measures
| Measure |
Placebo
n=49 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=53 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Minimum Observed Plasma Drug Concentrations at Steady State (Cmin,ss) of Palovarotene
|
0.314 ng/mL
Geometric Coefficient of Variation 86.1
|
0.674 ng/mL
Geometric Coefficient of Variation 83.3
|
—
|
SECONDARY outcome
Timeframe: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dosePopulation: The PKS included participants receiving treatment with palovarotene and with evaluable PK data.
The Tmax,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Outcome measures
| Measure |
Placebo
n=49 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=52 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Time to Maximum Observed Drug Concentration at Steady State (Tmax,ss) of Palovarotene
|
3.00 hour
Interval 2.47 to 10.0
|
3.01 hour
Interval 2.42 to 24.25
|
—
|
SECONDARY outcome
Timeframe: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dosePopulation: The PKS included participants receiving treatment with palovarotene and with evaluable PK data.
The AUC0-24,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=46 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve at Steady State From Time 0 to 24 Hours After Dosing (AUC0-24,ss) of Palovarotene
|
112 hour*ng/mL
Geometric Coefficient of Variation 29.1
|
241 hour*ng/mL
Geometric Coefficient of Variation 42.7
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Month 1Population: The Safety set included randomized participants who received at least 1 dose of study drug. Only data from the participants analyzed at Day 1 and Month 1 were included in the analysis.
Palatability of palovarotene and placebo when sprinkled on specific foods as assessed with a 5-point hedonic face scale at the first dose (Day 1) and at Month 1 in all participants (including \<4 years old) who sprinkled the palovarotene or placebo onto a spoonful of specific foods. The hedonic face scale ranges from 1 to 5 where, 1= dislike very much, 2= dislike slightly, 3= neither like nor dislike, 4= like slightly, 5= like very much. Higher scores indicate positive outcome.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=15 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=11 Participants
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Day 1 · Dislike a little
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Day 1 · Dislike very much
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Day 1 · Not sure
|
6 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Day 1 · Like a little
|
3 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Day 1 · Like very much
|
11 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Month 1 · Dislike very much
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Month 1 · Dislike a little
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Month 1 · Not sure
|
5 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Month 1 · Like a little
|
8 Participants
|
5 Participants
|
1 Participants
|
|
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Month 1 · Like very much
|
6 Participants
|
8 Participants
|
6 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
Palovarotene 2.5 mg
Serious events: 2 serious events
Other events: 56 other events
Deaths: 0 deaths
Palovarotene 5.0 mg
Serious events: 2 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=62 participants at risk
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=66 participants at risk
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=65 participants at risk
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Blood Loss Anaemia
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
0.00%
0/66 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/65 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/66 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
0.00%
0/65 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Radius Fracture
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/66 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
0.00%
0/65 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Ulna Fracture
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/66 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
0.00%
0/65 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Status Epilepticus
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
0.00%
0/66 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/65 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=62 participants at risk
Participants were to receive placebo matching with palovarotene capsules orally once daily, for up to 24 months.
|
Palovarotene 2.5 mg
n=66 participants at risk
Participants were to receive weight-adjusted dose equivalent of palovarotene 2.5 mg capsules orally once daily, for up to 24 months.
|
Palovarotene 5.0 mg
n=65 participants at risk
Participants were to receive weight-adjusted dose equivalent of palovarotene 5.0 mg capsules orally once daily, for up to 24 months.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
11.3%
7/62 • Number of events 12 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
25.8%
17/66 • Number of events 31 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
38.5%
25/65 • Number of events 50 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
11.3%
7/62 • Number of events 9 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
24.2%
16/66 • Number of events 19 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
29.2%
19/65 • Number of events 23 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.7%
6/62 • Number of events 7 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
12.1%
8/66 • Number of events 9 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
10.8%
7/65 • Number of events 9 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash Generalised
|
3.2%
2/62 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.5%
3/66 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
7.7%
5/65 • Number of events 5 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Lip Dry
|
4.8%
3/62 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
9.1%
6/66 • Number of events 6 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
16.9%
11/65 • Number of events 11 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
2/62 • Number of events 2 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.5%
3/66 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
10.8%
7/65 • Number of events 9 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Dry Mouth
|
4.8%
3/62 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
6.1%
4/66 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
6.2%
4/65 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
4.8%
3/62 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.5%
3/66 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
7.7%
5/65 • Number of events 6 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.3%
7/62 • Number of events 10 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.5%
3/66 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
1.5%
1/65 • Number of events 1 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
General disorders
Pyrexia
|
0.00%
0/62 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.5%
3/66 • Number of events 3 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
13.8%
9/65 • Number of events 9 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
9.7%
6/62 • Number of events 8 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
6.1%
4/66 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
4.6%
3/65 • Number of events 4 • Treatment-emergent adverse events were to be collected from the start of the first study drug (Day 1) up to 7 days after last study drug intake, assessed until data cut-off for study termination (maximum of 595 days).
The Safety set included randomized participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place