Trial Outcomes & Findings for Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of PTH Analog Tablets in Postmenopausal Women (NCT NCT01321723)

NCT ID: NCT01321723

Last Updated: 2013-03-01

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

97 participants

Primary outcome timeframe

24 weeks from baseline

Results posted on

2013-03-01

Participant Flow

Participant milestones

Participant milestones
Measure	Forsteo (Teriparatide) Teriparatide : 20 mcg SC Injection, once daily.	PTH Analog Tablets PTH analog : 5 mg tablets, once daily.	Placebo Placebo : matching tablets, once daily
Overall Study STARTED	32	33	32
Overall Study COMPLETED	27	28	28
Overall Study NOT COMPLETED	5	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Forsteo (Teriparatide) Teriparatide : 20 mcg SC Injection, once daily.	PTH Analog Tablets PTH analog : 5 mg tablets, once daily.	Placebo Placebo : matching tablets, once daily
Overall Study Adverse Event	3	5	2
Overall Study Withdrawal by Subject	2	0	2

Baseline Characteristics

Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of PTH Analog Tablets in Postmenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Forsteo (Teriparatide) n=32 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=33 Participants PTH analog : 5 mg tablets, once daily	Placebo n=32 Participants Placebo : matching tablets, once daily	Total n=97 Participants Total of all reporting groups
Age Continuous	66.5 years STANDARD_DEVIATION 6.99 • n=5 Participants	67.4 years STANDARD_DEVIATION 3.95 • n=7 Participants	66.1 years STANDARD_DEVIATION 6.09 • n=5 Participants	66.7 years STANDARD_DEVIATION 5.77 • n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	97 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 24 weeks from baseline

Population: mITT Population: all subjects who received at least one dose of treatment and at least one post-baseline BMD value. Missing data imputation for patients who completed Week 12 but not the full 24-week period, data was imputed using the LOCF. No data imputation was performed for Week 24, if the Week 12 data was missing.

Outcome measures

Outcome measures
Measure	Forsteo (Teriparatide) n=30 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=28 Participants PTH analog : 5 mg tablets, once daily	Placebo n=27 Participants Placebo : matching tablets, once daily
% Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24	5.07 percentage of change Standard Deviation 3.543	2.21 percentage of change Standard Deviation 2.503	-0.17 percentage of change Standard Deviation 2.739

SECONDARY outcome

Timeframe: 24 weeks from baseline

Serum collagen type I (CTx-1) fragments generated during osteoclastic bone turnover are biomarkers for bone resorption. β-CrossLaps electrochemiluminescent sandwich immunoassay was used.

Outcome measures

Outcome measures
Measure	Forsteo (Teriparatide) n=30 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=28 Participants PTH analog : 5 mg tablets, once daily	Placebo n=28 Participants Placebo : matching tablets, once daily
% Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24	113.32 percentage of change Standard Deviation 102.932	12.72 percentage of change Standard Deviation 36.547	15.13 percentage of change Standard Deviation 23.940

SECONDARY outcome

Timeframe: 24 weeks

AUC: (PTH analog tablets timepoints - baseline to 5.75 hours) (Forsteo injection timepoints - baseline to 2 hours)

Outcome measures

Outcome measures
Measure	Forsteo (Teriparatide) n=27 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=28 Participants PTH analog : 5 mg tablets, once daily	Placebo Placebo : matching tablets, once daily
Systemic Absorption of PTH at Week 24	152 pg* hr/mL Standard Deviation 65.7	165 pg* hr/mL Standard Deviation 180	—

SECONDARY outcome

Timeframe: 24 weeks from baseline

Outcome measures

Outcome measures
Measure	Forsteo (Teriparatide) n=30 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=28 Participants PTH analog : 5 mg tablets, once daily	Placebo n=28 Participants Placebo : matching tablets, once daily
% Change From Baseline in Bone Formation Marker (P1NP) at Week 24	210.07 percentage of change Standard Deviation 202.613	12.05 percentage of change Standard Deviation 37.055	-1.75 percentage of change Standard Deviation 27.459

POST_HOC outcome

Timeframe: 24 weeks

Population: Overall Summary of Adverse Events - Each subject with an event is counted only once although they may have several events.

Outcome measures

Outcome measures
Measure	Forsteo (Teriparatide) n=32 Participants Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=33 Participants PTH analog : 5 mg tablets, once daily	Placebo n=32 Participants Placebo : matching tablets, once daily
Number of Participants With AEs as a Measure of Safety and Tolerability	23 participants	30 participants	21 participants

Adverse Events

Forsteo (Teriparatide)

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

PTH Analog Tablets

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Forsteo (Teriparatide) n=32 participants at risk Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=33 participants at risk PTH analog : 5 mg tablets, once daily	Placebo n=32 participants at risk Placebo : matching tablets, once daily
Cardiac disorders Atrial flutter	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Nervous system disorders Headache	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.

Other adverse events

Additional Information

Nozer Mehta, PhD. Chief Scientific Officer

Unigene Laboratories, Inc.

Phone: (973) 265-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Forsteo (Teriparatide) n=32 participants at risk Teriparatide : 20 mcg SC Injection, once daily	PTH Analog Tablets n=33 participants at risk PTH analog : 5 mg tablets, once daily	Placebo n=32 participants at risk Placebo : matching tablets, once daily
Gastrointestinal disorders Abdominal pain	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	18.2% 6/33 • Number of events 6 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	39.4% 13/33 • Number of events 13 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	18.8% 6/32 • Number of events 6 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Musculoskeletal and connective tissue disorders Back pain	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.1% 2/33 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Cardiac disorders Bradycardia	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.1% 3/33 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Injury, poisoning and procedural complications Contusion	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Vascular disorders Dizziness	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.1% 3/33 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
General disorders Fatigue	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Nervous system disorders Headache	12.5% 4/32 • Number of events 4 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.1% 3/33 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Vascular disorders Hot flush	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.1% 3/33 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Vascular disorders Hypertension	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.1% 2/33 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Vascular disorders Hypotension	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	12.1% 4/33 • Number of events 4 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Infections and infestations Nasopharyngitis	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.1% 3/33 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Gastrointestinal disorders Nausea	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	15.2% 5/33 • Number of events 5 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	9.4% 3/32 • Number of events 3 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/33 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Cardiac disorders Presyncope	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Infections and infestations Rhinitis	6.2% 2/32 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.0% 1/33 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	3.1% 1/32 • Number of events 1 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Cardiac disorders Syncope	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	12.1% 4/33 • Number of events 4 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.
Ear and labyrinth disorders Vertigo	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	6.1% 2/33 • Number of events 2 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.	0.00% 0/32 • All AEs were recorded in the CRF during the course of the study. Serious adverse events (SAEs) were reported to the Sponsor within 24 hours of awareness. The occurrences of AEs were documented at each visit during the study.