Trial Outcomes & Findings for Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628) (NCT NCT00686699)

Last Updated: 2018-11-09

Results Overview

The ESRS total score consists of 4 subscales: 1) a questionnaire of extrapyramidal symptoms (EPS) and drug-induced movement disorders (DIMD) over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). The ESRS total score could range from 0 to 225, with a lower score reflecting a better outcome. The lowest ESRS total score for each participant within the 6-hour range on Day 14 was analyzed.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 6 hours post-dose on Day 14

Results posted on

2018-11-09

Participant Flow

Participant milestones

Participant milestones
Measure	Preladenant 25 mg BID→Placebo BID Participants received one preladenant 25 mg capsule twice daily (BID) for 14 days during the first treatment period and received one matching placebo capsule BID during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.	Placebo BID→Preladenant 25 mg BID Participants received one matching placebo capsule BID for 14 days during the first treatment period and received one preladenant 25 mg capsule during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.
Treatment Period 1 STARTED	4	7
Treatment Period 1 COMPLETED	4	5
Treatment Period 1 NOT COMPLETED	0	2
Treatment Period 2 STARTED	4	5
Treatment Period 2 COMPLETED	4	5
Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Preladenant 25 mg BID→Placebo BID Participants received one preladenant 25 mg capsule twice daily (BID) for 14 days during the first treatment period and received one matching placebo capsule BID during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.	Placebo BID→Preladenant 25 mg BID Participants received one matching placebo capsule BID for 14 days during the first treatment period and received one preladenant 25 mg capsule during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.
Treatment Period 1 Adverse Event	0	2

Baseline Characteristics

Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Preladenant 25 mg BID→Placebo BID n=4 Participants Participants received one preladenant 25 mg capsule BID for 14 days during the first treatment period and received one matching placebo capsule BID during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.	Placebo BID→Preladenant 25 mg BID n=7 Participants Participants received one matching placebo capsule BID for 14 days during the first treatment period and received one preladenant 25 mg capsule during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.	Total n=11 Participants Total of all reporting groups
Age, Continuous	33.8 Years STANDARD_DEVIATION 8.5 • n=5 Participants	46.0 Years STANDARD_DEVIATION 13.2 • n=7 Participants	41.5 Years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 hours post-dose on Day 14

Population: Consisted of all participants who received both treatments \& had Day 14 ESRS scores from both treatment periods.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 Participants Participants received one matching placebo capsule BID for 14 days.
Lowest Extrapyramidal Symptom Rating Score (ESRS) Total Score Within the 6-hour Evaluation on Day 14 of Each Treatment Period Day 14 (n=9, 9)	9.56 Score on a scale Standard Deviation 6.64	10.89 Score on a scale Standard Deviation 7.57
Lowest Extrapyramidal Symptom Rating Score (ESRS) Total Score Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline (n=9, 11)	14.22 Score on a scale Standard Deviation 6.24	17.18 Score on a scale Standard Deviation 11.03

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Population: Consisted of all participants who had a Baseline value and at least one post-Baseline value at each time point for Day 14 ESRS scores from both treatment periods. Therefore Baseline includes only participants who had corresponding data on Day 14.

The ESRS total score consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). The ESRS total score could range from 0 to 225, with a lower score reflecting a better outcome. The mean ESRS total scores at Hours 1, 2, 3, 4, 5, and 6 on Day 14 were analyzed.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=9 Participants Participants received one matching placebo capsule BID for 14 days.
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline	21.0 Score on a scale Standard Deviation 8.6	20.7 Score on a scale Standard Deviation 15.8
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 1 hour post-dose	14.3 Score on a scale Standard Deviation 7.0	15.1 Score on a scale Standard Deviation 10.4
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 4 hours post-dose	12.8 Score on a scale Standard Deviation 6.7	14.1 Score on a scale Standard Deviation 10.8
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 5 hours post-dose	12.3 Score on a scale Standard Deviation 7.0	13.0 Score on a scale Standard Deviation 9.5
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 6 hours post-dose	11.8 Score on a scale Standard Deviation 6.7	11.8 Score on a scale Standard Deviation 7.3
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 2 hours post-dose	15.3 Score on a scale Standard Deviation 7.1	13.8 Score on a scale Standard Deviation 11.2
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period 3 hours post-dose	12.8 Score on a scale Standard Deviation 6.6	14.6 Score on a scale Standard Deviation 11.5

SECONDARY outcome

Timeframe: Up to 6 hours post-dose on Day 14

Population: Consisted of all participants who received both treatments \& had Day 14 ESRS scores from both treatment periods.

The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The lowest subscale score on Day 14 was analyzed.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 Participants Participants received one matching placebo capsule BID for 14 days.
Lowest ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline (n=9, 11)	2.67 Score on a scale Standard Deviation 1.41	3.00 Score on a scale Standard Deviation 2.24
Lowest ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period Day 14 (n=9, 9)	1.89 Score on a scale Standard Deviation 1.54	2.00 Score on a scale Standard Deviation 1.50

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=9 Participants Participants received one matching placebo capsule BID for 14 days.
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 3 hours post-dose	2.9 Score on a scale Standard Deviation 2.0	2.7 Score on a scale Standard Deviation 2.2
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 4 hours post-dose	2.7 Score on a scale Standard Deviation 1.9	2.4 Score on a scale Standard Deviation 2.2
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline	4.0 Score on a scale Standard Deviation 1.9	4.1 Score on a scale Standard Deviation 2.8
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 1 hour post-dose	2.9 Score on a scale Standard Deviation 1.8	2.8 Score on a scale Standard Deviation 2.4
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 2 hours post-dose	3.1 Score on a scale Standard Deviation 1.8	2.3 Score on a scale Standard Deviation 1.7
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 5 hours post-dose	2.6 Score on a scale Standard Deviation 1.7	2.7 Score on a scale Standard Deviation 2.2
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period 6 hours post-dose	2.6 Score on a scale Standard Deviation 1.7	2.2 Score on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: Up to 6 hours post-dose on Day 14

Population: Consisted of all participants who received both treatments \& had Day 14 ESRS scores from both treatment periods.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 Participants Participants received one matching placebo capsule BID for 14 days.
Lowest ESRS Part II Subscore: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline (n=9, 11)	7.22 Score on a scale Standard Deviation 5.04	8.91 Score on a scale Standard Deviation 6.79
Lowest ESRS Part II Subscore: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Day 14 (n=9, 9)	4.67 Score on a scale Standard Deviation 4.24	5.67 Score on a scale Standard Deviation 5.74

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=9 Participants Participants received one matching placebo capsule BID for 14 days.
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 5 hours post-dose	7.7 Score on a scale Standard Deviation 5.2	7.1 Score on a scale Standard Deviation 6.9
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 6 hours post-dose	6.8 Score on a scale Standard Deviation 4.7	6.7 Score on a scale Standard Deviation 6.3
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline	10.8 Score on a scale Standard Deviation 5.9	9.4 Score on a scale Standard Deviation 5.0
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 1 hour post-dose	8.1 Score on a scale Standard Deviation 5.6	8.1 Score on a scale Standard Deviation 6.7
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 2 hours post-dose	9.2 Score on a scale Standard Deviation 5.2	7.4 Score on a scale Standard Deviation 8.2
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 3 hours post-dose	7.3 Score on a scale Standard Deviation 5.0	8.0 Score on a scale Standard Deviation 7.8
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 4 hours post-dose	7.6 Score on a scale Standard Deviation 4.6	7.8 Score on a scale Standard Deviation 7.5

SECONDARY outcome

Timeframe: Up to 6 hours post-dose on Day 14

Population: Consisted of all participants who received both treatments \& had Day 14 ESRS scores from both treatment periods.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 Participants Participants received one matching placebo capsule BID for 14 days.
Lowest ESRS Part III Subscore: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline (n=9, 11)	1.56 Score on a scale Standard Deviation 2.79	2.09 Score on a scale Standard Deviation 4.57
Lowest ESRS Part III Subscore: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Day 14 (n=9, 9)	1.22 Score on a scale Standard Deviation 1.99	1.22 Score on a scale Standard Deviation 1.86

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=9 Participants Participants received one matching placebo capsule BID for 14 days.
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 1 hour post-dose	1.6 Score on a scale Standard Deviation 2.8	2.2 Score on a scale Standard Deviation 2.8
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 4 hours post-dose	1.3 Score on a scale Standard Deviation 2.2	2.0 Score on a scale Standard Deviation 2.7
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 5 hours post-dose	1.2 Score on a scale Standard Deviation 2.0	1.8 Score on a scale Standard Deviation 2.2
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 6 hours post-dose	1.2 Score on a scale Standard Deviation 2.0	1.3 Score on a scale Standard Deviation 2.1
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline	3.0 Score on a scale Standard Deviation 4.4	4.2 Score on a scale Standard Deviation 8.7
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 2 hours post-dose	1.4 Score on a scale Standard Deviation 2.5	2.0 Score on a scale Standard Deviation 2.6
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 3 hours post-dose	1.3 Score on a scale Standard Deviation 2.2	2.1 Score on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: Up to 6 hours post-dose on Day 14

Population: Consisted of all participants who received both treatments \& had Day 14 ESRS scores from both treatment periods.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 Participants Participants received one matching placebo capsule BID for 14 days.
Lowest ESRS Part IV Subscore: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline (n=9, 11)	2.00 Score on a scale Standard Deviation 3.84	2.18 Score on a scale Standard Deviation 4.12
Lowest ESRS Part IV Subscore: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Day 14 (n=9, 9)	0.89 Score on a scale Standard Deviation 2.32	1.22 Score on a scale Standard Deviation 1.99

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=9 Participants Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=9 Participants Participants received one matching placebo capsule BID for 14 days.
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period Baseline	3.2 Score on a scale Standard Deviation 6.4	2.9 Score on a scale Standard Deviation 6.5
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 3 hours post-dose	1.2 Score on a scale Standard Deviation 2.6	1.8 Score on a scale Standard Deviation 2.6
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 6 hours post-dose	1.2 Score on a scale Standard Deviation 2.6	1.6 Score on a scale Standard Deviation 2.4
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 1 hour post-dose	1.8 Score on a scale Standard Deviation 3.6	2.0 Score on a scale Standard Deviation 3.0
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 2 hours post-dose	1.6 Score on a scale Standard Deviation 2.9	2.0 Score on a scale Standard Deviation 3.0
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 4 hours post-dose	1.2 Score on a scale Standard Deviation 2.6	1.9 Score on a scale Standard Deviation 2.6
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period 5 hours post-dose	0.9 Score on a scale Standard Deviation 2.3	1.4 Score on a scale Standard Deviation 2.1

Adverse Events

Preladenant 25 mg BID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo BID

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Preladenant 25 mg BID n=9 participants at risk Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 participants at risk Participants received one matching placebo capsule BID for 14 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders Nausea	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders Vomiting	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The principal investigator agrees to provide to the sponsor 30 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Preladenant 25 mg BID n=9 participants at risk Participants received one preladenant 25 mg capsule BID for 14 days.	Placebo BID n=11 participants at risk Participants received one matching placebo capsule BID for 14 days.
Cardiac disorders Tachycardia	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders Constipation	22.2% 2/9 • Number of events 4 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders Fatigue	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	18.2% 2/11 • Number of events 2 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders Feeling hot	11.1% 1/9 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations Nasopharyngitis	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations Rhinitis	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations Tracheitis	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Nervous system disorders Burning sensation	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Anxiety	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Crying	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Depression	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Fear	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Insomnia	11.1% 1/9 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Sleep disorder	11.1% 1/9 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/11 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders Suicidal ideation	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Reproductive system and breast disorders Breast discomfort	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/9 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	9.1% 1/11 • Number of events 1 • Up to 1 week after the last dose of study drug in a treatment period (Up to 8 weeks) The safety population consisted of all participants who received at least one dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.