Trial Outcomes & Findings for Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone (NCT NCT02381288)

Last Updated: 2017-05-17

Results Overview

Cav is the average serum concentration of the dosing interval, calculated as area under the effect curve (AUEC) divided by the duration of the dosing interval.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Once-daily regimen Day 42; Twice-weekly regimen Day 39; Once-weekly regimen Day 36

Results posted on

2017-05-17

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 10 September 2015 to 08 April 2016.

Middle-aged and older male participants with low testosterone levels were enrolled in once daily TAK-448 0.1 µg, twice weekly TAK-448 0.3 µg, once weekly TAK-448 1 µg or Placebo groups.

Participant milestones

Participant milestones
Measure	Placebo TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.
Overall Study STARTED	5	2	5	5
Overall Study COMPLETED	5	2	5	5
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=5 Participants TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg n=2 Participants TAK-448 0.1 µg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg n=5 Participants TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg n=5 Participants TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.	Total n=17 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 3.24 • n=5 Participants	71.0 years STANDARD_DEVIATION 11.31 • n=7 Participants	70.6 years STANDARD_DEVIATION 9.32 • n=5 Participants	65.2 years STANDARD_DEVIATION 1.48 • n=4 Participants	67.1 years STANDARD_DEVIATION 6.54 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Race/Ethnicity, Customized Non-Hispanic and Latino	5 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	17 participants n=21 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized White	5 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	12 participants n=21 Participants
Region of Enrollment United States	5 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	17 participants n=21 Participants
Height	173.6 cm STANDARD_DEVIATION 5.81 • n=5 Participants	173.5 cm STANDARD_DEVIATION 3.54 • n=7 Participants	172.4 cm STANDARD_DEVIATION 7.80 • n=5 Participants	174.6 cm STANDARD_DEVIATION 6.77 • n=4 Participants	173.5 cm STANDARD_DEVIATION 6.05 • n=21 Participants
Weight	93.0 kg STANDARD_DEVIATION 16.6 • n=5 Participants	101.6 kg STANDARD_DEVIATION 11.3 • n=7 Participants	99.4 kg STANDARD_DEVIATION 17.3 • n=5 Participants	91.5 kg STANDARD_DEVIATION 21.5 • n=4 Participants	95.5 kg STANDARD_DEVIATION 16.8 • n=21 Participants
Baseline Body Mass Index (BMI)	30.7 kg/m^2 STANDARD_DEVIATION 4.3 • n=5 Participants	33.9 kg/m^2 STANDARD_DEVIATION 5.2 • n=7 Participants	33.3 kg/m^2 STANDARD_DEVIATION 4.2 • n=5 Participants	30.0 kg/m^2 STANDARD_DEVIATION 6.5 • n=4 Participants	31.6 kg/m^2 STANDARD_DEVIATION 4.9 • n=21 Participants
Smoking Classification Participant has never smoked	3 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	11 participants n=21 Participants
Smoking Classification Participant is an ex-smoker	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	6 participants n=21 Participants
Alcohol Classification Participant has never drunk	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Alcohol Classification Participant is a current drinker	3 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	5 participants n=4 Participants	12 participants n=21 Participants
Alcohol Classification Participant is an ex-drinker	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Caffeine Consumption Yes	3 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	12 participants n=21 Participants
Caffeine Consumption No	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	5 participants n=21 Participants

PRIMARY outcome

Timeframe: Once-daily regimen Day 42; Twice-weekly regimen Day 39; Once-weekly regimen Day 36

Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study drug or placebo and who had at least 1 valid PD measure.

Cav is the average serum concentration of the dosing interval, calculated as area under the effect curve (AUEC) divided by the duration of the dosing interval.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg n=2 Participants TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg n=5 Participants TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg n=5 Participants TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.
Percent Change From Baseline in Average Serum Concentration (Cav) of Total ST After 6 Weeks of Dosing	14.32 percent change Standard Deviation 29.186	7.100 percent change Standard Deviation 18.102	10.60 percent change Standard Deviation 12.594	15.80 percent change Standard Deviation 26.531

PRIMARY outcome

Timeframe: Once-daily regimen Day 42; Twice-weekly regimen Day 39; Once-weekly regimen Day 36

Population: PD analysis set included all participants who received at least 1 dose of study drug or placebo and who had at least 1 valid PD measure. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.

Trough serum concentration of total and free ST, defined as lowest Baseline concentration.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg n=2 Participants TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg n=4 Participants TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg n=5 Participants TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.
Trough Serum Concentration (Ctrough) of ST	285.4 ng/dL Standard Deviation 94.952	255.5 ng/dL Standard Deviation 102.53	135.3 ng/dL Standard Deviation 44.515	244.4 ng/dL Standard Deviation 61.756

SECONDARY outcome

Timeframe: Day 1 (first dose) and Day 42 for once-daily regimen, Day 39 for twice-weekly regimen, or Day 36 for once-weekly regimen (last dose)

Population: PD analysis set included all participants who received at least 1 dose of study drug or placebo and who have at least 1 valid PD measure.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Assessments were done Day 1 and Day 42 for once daily regimen, on Day 36 for once weekly regimen and on Day 39 for twice-weekly regimen (Day 42/36/39).

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg n=2 Participants TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg n=5 Participants TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg n=5 Participants TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.
Serum Testosterone Cmax: Maximum Observed Plasma Concentration Day 1	287.6 ng/dL Standard Deviation 58.518	306.5 ng/dL Standard Deviation 68.589	351.2 ng/dL Standard Deviation 87.434	427.8 ng/dL Standard Deviation 67.054
Serum Testosterone Cmax: Maximum Observed Plasma Concentration Day 42/36/39	354.8 ng/dL Standard Deviation 136.09	287.0 ng/dL Standard Deviation 57.983	263.8 ng/dL Standard Deviation 82.914	343.0 ng/dL Standard Deviation 57.524

SECONDARY outcome

Timeframe: Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.

Population: Due to early termination of the study pharmacokinetic data was not collected and reported.

Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.

Population: Due to early termination of the study pharmacokinetic data was not collected and reported.

Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Once-daily Dosing Days 1 and 42, Twice-weekly Dosing Days 1 and 39, Once-weekly Dosing Days 1 and 36, predose and at multiple time intervals (up to 8 hours) post-dose.

Population: Due to early termination of the study pharmacokinetic data was not collected and reported.

T1/2 is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

TAK-448 0.1 µg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

TAK-448 0.3 µg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

TAK-448 1.0 µg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Placebo n=5 participants at risk TAK-448 placebo matching injection, subcutaneously, either once daily on Days 1 through 42, or twice weekly on Days 1 through 39 or once weekly on Days 1 through 36.	TAK-448 0.1 µg n=2 participants at risk TAK-448 0.1 mcg, injection, subcutaneously, once daily on Days 1 through 42.	TAK-448 0.3 µg n=5 participants at risk TAK-448 0.3 µg, injection, subcutaneously, twice-weekly on Days 1 through 39.	TAK-448 1.0 µg n=5 participants at risk TAK-448 1.0 µg, injection, subcutaneously, once-weekly on Days 1 through 36.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 1/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Flatulence	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Tooth infection	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Feeling abnormal	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Palpitations	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Lacrimation increased	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Urinary incontinence	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Phlebitis	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/2 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 1/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/5 • Baseline up to Day 56 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.