Trial Outcomes & Findings for Pharmacokinetic Study of Testosterone Enanthate (NCT NCT01887418)

Last Updated: 2018-01-11

Results Overview

The area under the curve from time zero to last quantifiable concentration \[AUC (0-t)\] of TE administered by SC injection once weekly at doses of 50 mg and 100 mg via the QST

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

39 participants

Primary outcome timeframe

0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose, at 6 Weeks

Results posted on

2018-01-11

Participant Flow

Subjects were screened at 10 sites in USA. In total, 39 eligible subjects were enrolled and received study medication (investigational SC QST or IM RLD): 14 subjects in 50 mg SC QST arm, 15 subjects in 100 mg SC QST arm and 10 subjects in 200 mg IM RLD arm.

Eligible patients were randomized to receive SC 50mg (Treatment B) or SC 100mg (Treatment A) QST and the subject who were on IM testosterone replacement therapy, received IM TE RLD (Treatment C).

Participant milestones

Participant milestones
Measure	QuickShot™ - 100 mg Treatment A QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone once a week	QuickShot™ - 50 mg Treatment B QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone once a week.	Delatestryl 200 mg IM Treatment C Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: injected once only
Overall Study STARTED	15	14	10
Overall Study COMPLETED	15	14	9
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	QuickShot™ - 100 mg Treatment A QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone once a week	QuickShot™ - 50 mg Treatment B QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone once a week.	Delatestryl 200 mg IM Treatment C Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: injected once only
Overall Study Travelling difficulties	0	0	1

Baseline Characteristics

Pharmacokinetic Study of Testosterone Enanthate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QuickShot™ - 100 mg Treatment A n=15 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone once a week for 6 weeks	QuickShot™ - 50 mg Treatment B n=14 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone once a week for 6 weeks	Delatestryl 200 mg IM Treatment C n=10 Participants Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: injected once only	Total n=39 Participants Total of all reporting groups
Age, Continuous	54.7 years STANDARD_DEVIATION 12.80 • n=5 Participants	54.0 years STANDARD_DEVIATION 12.42 • n=7 Participants	48.9 years STANDARD_DEVIATION 10.94 • n=5 Participants	52.9 years STANDARD_DEVIATION 12.14 • n=4 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
Sex: Female, Male Male	15 Participants n=5 Participants	14 Participants n=7 Participants	10 Participants n=5 Participants	39 Participants n=4 Participants
Race/Ethnicity, Customized White	13 participants n=5 Participants	14 participants n=7 Participants	8 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized African American	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment United States	15 participants n=5 Participants	14 participants n=7 Participants	10 participants n=5 Participants	39 participants n=4 Participants
Body Mass Index (BMI) at screening (kg/m^2)	29.19 kg/m^2 STANDARD_DEVIATION 2.87 • n=5 Participants	28.51 kg/m^2 STANDARD_DEVIATION 2.17 • n=7 Participants	29.05 kg/m^2 STANDARD_DEVIATION 2.21 • n=5 Participants	28.91 kg/m^2 STANDARD_DEVIATION 2.43 • n=4 Participants
Baseline Total Testosterone (TT) (ng/dL)	201.50 ng/dL STANDARD_DEVIATION 71.53 • n=5 Participants	214.64 ng/dL STANDARD_DEVIATION 59.05 • n=7 Participants	735.10 ng/dL STANDARD_DEVIATION 187.96 • n=5 Participants	343.04 ng/dL STANDARD_DEVIATION 256.67 • n=4 Participants

PRIMARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose, at 6 Weeks

Population: PK profile of TT obtained at Week 6 of treatment by QST

The area under the curve from time zero to last quantifiable concentration \[AUC (0-t)\] of TE administered by SC injection once weekly at doses of 50 mg and 100 mg via the QST

Outcome measures

Outcome measures
Measure	QuickShot™ - 100 mg Treatment A n=15 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone	QuickShot™ - 50 mg Treatment B n=14 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone	Delatestryl 200 mg IM Treatment C n=10 Participants Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: Standard of care
The Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Testosterone Enanthate Formulations at 6 Weeks	150445.2 ng*hr/dL Standard Deviation 46998.76	70955.7 ng*hr/dL Standard Deviation 20815.18	278657.9 ng*hr/dL Standard Deviation 168295.52

PRIMARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose, at 6 Weeks

Population: PK profile of TT obtained at Week 6 of treatment by QST

The maximum observed plasma concentration \[Cmax\] of TE administered by SC injection once weekly at doses of 50 mg and 100 mg via the QST

Outcome measures

Outcome measures
Measure	QuickShot™ - 100 mg Treatment A n=15 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone	QuickShot™ - 50 mg Treatment B n=14 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone	Delatestryl 200 mg IM Treatment C n=10 Participants Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: Standard of care
The Maximum Plasma Concentration [Cmax] of Testosterone Enanthate Formulations at 6 Weeks	1345.6 ng/dL Standard Deviation 435.63	622.4 ng/dL Standard Deviation 129.51	261.9 ng/dL Standard Deviation 1310.34

PRIMARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose, at 6 Weeks

Population: PK profile of TT obtained at Week 6 of treatment by QST

The average concentration \[Cavg\] of TE administered by SC injection once weekly at doses of 50 mg and 100 mg via the QST

Outcome measures

Outcome measures
Measure	QuickShot™ - 100 mg Treatment A n=15 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone	QuickShot™ - 50 mg Treatment B n=14 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone	Delatestryl 200 mg IM Treatment C n=10 Participants Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: Standard of care
The Average Concentration [Cavg] of Testosterone Enanthate Formulations at 6 Weeks	895.5 ng/dL Standard Deviation 279.75	422.4 ng/dL Standard Deviation 123.90	1658.7 ng/dL Standard Deviation 1001.76

SECONDARY outcome

Timeframe: 6 weeks

The number of TT Cavg (0-168h) values within the normal range (300-1100 ng/dL) following treatment with SC TE administered via QST or IM TE

Outcome measures

Outcome measures
Measure	QuickShot™ - 100 mg Treatment A n=15 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone	QuickShot™ - 50 mg Treatment B n=14 Participants QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone	Delatestryl 200 mg IM Treatment C n=10 Participants Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: Standard of care
Number of Patients in the PK Parameter Category	10 participants	12 participants	3 participants

Adverse Events

QuickShot™ - 100 mg Treatment A

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

QuickShot™ - 50 mg Treatment B

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Delatestryl 200 mg IM Treatment C

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jonathan Jaffe, MD; Vice President Clinical Development

Antares Pharma Inc.

Phone: 609-329-3020

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Other adverse events
Measure	QuickShot™ - 100 mg Treatment A n=15 participants at risk QuickShot™ - Auto-injector device for SC use QuickShot™ - 100 mg Treatment A: QuickShot™ for the delivery of testosterone once a week	QuickShot™ - 50 mg Treatment B n=14 participants at risk QuickShot™ - Auto-injector device for SC use QuickShot™ - 50 mg Treatment B: QuickShot™ for the delivery of testosterone once a week.	Delatestryl 200 mg IM Treatment C n=10 participants at risk Commercially available Testosterone enanthate 200 mg IM dosage - 'standard of care' arm for reference Delatestryl 200 mg IM Treatment C: injected once only
Gastrointestinal disorders Diarrhea	0.00% 0/15 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
General disorders Vessel puncture site hematoma	13.3% 2/15 • Number of events 2 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
General disorders Injection site hemorrhage*	0.00% 0/15 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Infections and infestations Upper respiratory tract infection	13.3% 2/15 • Number of events 2 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Infections and infestations Bronchitis	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Infections and infestations Pneumonia	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Infections and infestations Sinusitis	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Infections and infestations Tooth infection	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/15 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Injury, poisoning and procedural complications Procedural pain	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Investigations Blood triglycerides increased	0.00% 0/15 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Investigations C-reactive protein increased	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Investigations Prostatic specific antigen increased	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Musculoskeletal and connective tissue disorders Neck pain	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Nervous system disorders Headache	0.00% 0/15 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Psychiatric disorders Insomnia	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	7.1% 1/14 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 2/15 • Number of events 2 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.
Skin and subcutaneous tissue disorders Acne	6.7% 1/15 • Number of events 1 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/14 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.	0.00% 0/10 • Adverse events were classified as any adverse events that occurred from Day1 (after screening) to a given treatment period until the subject completed the study. The duration of the study participation for subjects was approximately 19 weeks. The Safety Population was defined as all randomized subjects who received at least 1 dose of investigational product. The safety population was 39 subjects.