Trial Outcomes & Findings for A Study to Assess Menstrual Cramp Pain Associated With Primary Dysmenorrhea (NCT NCT03448536)

Last Updated: 2019-10-28

Results Overview

Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value is 0, and the maximum value is 46. Higher scores was indicative of more pain relief.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

201 participants

Primary outcome timeframe

Up to 12 hours post-dose

Results posted on

2019-10-28

Participant Flow

Study was conducted at multiple centers in the US between 05 April 2018 (first patient first visit) and 05 September 2018 (last patient last visit).

Overall, 242 participants were screened. Of them, 201 participants were randomized, and 196 received study treatment.

Participant milestones

Participant milestones
Measure	Naproxen Sodium : Acetaminophen Participants received one single oral dose of 440 mg naproxen sodium in treatment period 1, followed by one single oral dose of 1000 mg acetaminophen in treatment period 2	Acetaminophen : Naproxen Sodium Participants received one single oral dose of 1000 mg acetaminophen in treatment period 1, followed by one single oral dose of 440 mg naproxen sodium in treatment period 2
Overall Study STARTED	100	101
Overall Study Completed First Intervention	95	97
Overall Study Completed Second Intervention	82	87
Overall Study COMPLETED	88	97
Overall Study NOT COMPLETED	12	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Naproxen Sodium : Acetaminophen Participants received one single oral dose of 440 mg naproxen sodium in treatment period 1, followed by one single oral dose of 1000 mg acetaminophen in treatment period 2	Acetaminophen : Naproxen Sodium Participants received one single oral dose of 1000 mg acetaminophen in treatment period 1, followed by one single oral dose of 440 mg naproxen sodium in treatment period 2
Overall Study Protocol Violation	2	0
Overall Study Pregnancy	1	0
Overall Study Withdrawal by Subject	1	2
Overall Study Lost to Follow-up	3	2
Overall Study Inadequate pain reporter	1	0
Overall Study Other	3	0
Overall Study Physician Decision	1	0

Baseline Characteristics

A Study to Assess Menstrual Cramp Pain Associated With Primary Dysmenorrhea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Naproxen Sodium : Acetaminophen n=96 Participants Participants received one single oral dose of 440 mg naproxen sodium in treatment period 1, followed by one single oral dose of 1000 mg acetaminophen in treatment period 2	Acetaminophen : Naproxen Sodium n=100 Participants Participants received one single oral dose of 1000 mg acetaminophen in treatment period 1, followed by one single oral dose of 440 mg naproxen sodium in treatment period 2	Total n=196 Participants Total of all reporting groups
Age, Continuous	24.7 years STANDARD_DEVIATION 5.60 • n=5 Participants	25.0 years STANDARD_DEVIATION 5.77 • n=7 Participants	24.8 years STANDARD_DEVIATION 5.67 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	100 Participants n=7 Participants	196 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	83 Participants n=5 Participants	85 Participants n=7 Participants	168 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	68 Participants n=7 Participants	134 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
At least moderate pain intensity during 4 of last 6 menstrual cycles Yes	96 Participants n=5 Participants	100 Participants n=7 Participants	196 Participants n=5 Participants
At least moderate pain intensity during 4 of last 6 menstrual cycles No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 hours post-dose

Population: PP population per treatment received (included all participants who were randomized and provided at least one measure of an efficacy parameter after the first dose of investigational medicinal product \[IMP\] without any major protocol violations)

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
Sum of Total Pain Relief (TOTPAR) Over 0-12 Hours	29.18 Scores on a scale * hours Standard Error 1.003	24.87 Scores on a scale * hours Standard Error 1.029

SECONDARY outcome

Timeframe: Up to 12 hours post-dose

Population: PP population per treatment received

Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted summed pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value could be -115, and the maximum value could be 115.

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
Summed Pain Intensity Difference (SPID) Over 0-12 Hours	53.62 Scores on a scale * hours Standard Error 1.931	43.82 Scores on a scale * hours Standard Error 1.977

SECONDARY outcome

Timeframe: Up to 6 hours post-dose

Population: PP population per treatment received

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
SPID Over 0-6 Hours	23.47 Scores on a scale * hours Standard Error 0.902	21.94 Scores on a scale * hours Standard Error 0.925

SECONDARY outcome

Timeframe: From 6 hours to 12 hours post-dose

Population: PP population per treatment received

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
SPID Over 6-12 Hours	30.15 Scores on a scale * hours Standard Error 1.252	21.88 Scores on a scale * hours Standard Error 1.280

SECONDARY outcome

Timeframe: Up to 6 hours post-dose

Population: PP population per treatment received

Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value is 0, and the maximum value is 22. Higher scores was indicative of more pain relief.

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
TOTPAR Over 0-6 Hours	13.46 Scores on a scale * hours Standard Error 0.451	12.90 Scores on a scale * hours Standard Error 0.463

SECONDARY outcome

Timeframe: From 6 hours to 12 hours post-dose

Population: PP population per treatment received

Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. The minimum value is 0, and the maximum value is 24. Higher scores was indicative of more pain relief.

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
TOTPAR 6-12 Hours	15.72 Scores on a scale * hours Standard Error 0.661	11.97 Scores on a scale * hours Standard Error 0.677

SECONDARY outcome

Timeframe: Up to 12 hours post-dose

Population: PP population per treatment received

Time to first intake of rescue medication was defined as the number of hours elapsed between time of dose and time of rescue medication in each treatment period. Participants would be censored at time of last pain assessment.

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
Time to First Intake of Rescue Medication	NA Hours Insufficient number of participants with events to estimate the median and its confidence limits using the model	NA Hours Insufficient number of participants with events to estimate the median and its confidence limits using the model

SECONDARY outcome

Timeframe: Up to 12 hours post-dose

Population: PP population per treatment received

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
Pain Intensity Difference (PID) Scores at Each Evaluation 30 minutes	0.8 Scores on a scale Standard Deviation 1.47	0.9 Scores on a scale Standard Deviation 1.61
Pain Intensity Difference (PID) Scores at Each Evaluation 1 hour	1.9 Scores on a scale Standard Deviation 1.93	2.1 Scores on a scale Standard Deviation 2.01
Pain Intensity Difference (PID) Scores at Each Evaluation 3 hours	4.1 Scores on a scale Standard Deviation 2.40	4.0 Scores on a scale Standard Deviation 2.68
Pain Intensity Difference (PID) Scores at Each Evaluation 6 hours	5.1 Scores on a scale Standard Deviation 2.59	4.3 Scores on a scale Standard Deviation 2.90
Pain Intensity Difference (PID) Scores at Each Evaluation 9 hours	4.9 Scores on a scale Standard Deviation 2.93	3.6 Scores on a scale Standard Deviation 3.13
Pain Intensity Difference (PID) Scores at Each Evaluation 12 hours	5.0 Scores on a scale Standard Deviation 2.97	3.5 Scores on a scale Standard Deviation 3.37

SECONDARY outcome

Timeframe: Up to 12 hours post-dose

Population: Subjects who were assessed for this endpoint in PP population per treatment received

Global evaluation was performed either at 12 hours post-dose or immediately prior to the first intake of rescue medication. Global Evaluation Score was based on the question 'Overall, I would rate the effectiveness of the study medication in relieving my menstrual pain as: 0=Poor, 1=Fair, 2=Good, 3=Very Good, 4=Excellent.'

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=156 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=156 Participants Participants received one single oral dose of 1000 mg acetaminophen
Number of Participants by Global Evaluation Scores Poor	10 Participants	13 Participants
Number of Participants by Global Evaluation Scores Fair	26 Participants	42 Participants
Number of Participants by Global Evaluation Scores Good	25 Participants	38 Participants
Number of Participants by Global Evaluation Scores Very good	60 Participants	38 Participants
Number of Participants by Global Evaluation Scores Excellent	35 Participants	25 Participants

SECONDARY outcome

Timeframe: Up to 12 hours post-dose

Population: PP population per treatment received

Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief).

Outcome measures

Outcome measures
Measure	Naproxen Sodium n=170 Participants Participants received one single oral dose of 440 mg naproxen sodium	Acetaminophen n=160 Participants Participants received one single oral dose of 1000 mg acetaminophen
Pain Relief Scores at Each Evaluation 30 minutes	0.9 Scores on a scale Standard Deviation 0.98	0.9 Scores on a scale Standard Deviation 1.01
Pain Relief Scores at Each Evaluation 1 hour	1.4 Scores on a scale Standard Deviation 1.06	1.6 Scores on a scale Standard Deviation 1.12
Pain Relief Scores at Each Evaluation 3 hours	2.3 Scores on a scale Standard Deviation 1.17	2.3 Scores on a scale Standard Deviation 1.32
Pain Relief Scores at Each Evaluation 6 hours	2.7 Scores on a scale Standard Deviation 1.45	2.4 Scores on a scale Standard Deviation 1.50
Pain Relief Scores at Each Evaluation 9 hours	2.6 Scores on a scale Standard Deviation 1.52	2.0 Scores on a scale Standard Deviation 1.57
Pain Relief Scores at Each Evaluation 12 hours	2.7 Scores on a scale Standard Deviation 1.60	1.9 Scores on a scale Standard Deviation 1.69

Adverse Events

Naproxen Sodium

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Acetaminophen

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Naproxen Sodium n=192 participants at risk Participants received one single oral dose of 440 mg naproxen sodium (safety population per treatment received)	Acetaminophen n=185 participants at risk Participants received one single oral dose of 1000 mg acetaminophen (safety population per treatment received)
Eye disorders Eye pruritus	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Gastrointestinal disorders Gastritis	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Gastrointestinal disorders Nausea	1.0% 2/192 • Number of events 2 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Gastrointestinal disorders Vomiting	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Infections and infestations Pharyngitis streptococcal	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	1.1% 2/185 • Number of events 2 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Infections and infestations Upper respiratory tract infection	1.6% 3/192 • Number of events 3 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Infections and infestations Urinary tract infection	0.00% 0/192 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Injury, poisoning and procedural complications Facial bones fracture	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Injury, poisoning and procedural complications Laceration	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Injury, poisoning and procedural complications Nail avulsion	0.00% 0/192 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Investigations Blood pressure increased	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/192 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Musculoskeletal and connective tissue disorders Back pain	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Nervous system disorders Dizziness	0.52% 1/192 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.00% 0/185 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Psychiatric disorders Attention deficit/hyperactivity disorder	0.00% 0/192 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/192 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.	0.54% 1/185 • Number of events 1 • The observation phase for adverse events (AEs) started with signing the informed consent form and ended in general with the last visit of follow-up (up to 133 days). After the end of follow-up there was no requirement to actively collect AEs. In case of ongoing AEs after the last follow-up visit - especially when related to treatment with the study medication - the respective AE was followed until resolution, if possible.