Trial Outcomes & Findings for Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis (NCT NCT00439244)

Last Updated: 2011-04-20

Results Overview

BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

412 participants

Primary outcome timeframe

Baseline through Week 52

Results posted on

2011-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	Zoledronic Acid Plus Teriparatide Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Overall Study STARTED	137	137	138
Overall Study Safety Population	137	137	137
Overall Study COMPLETED	126	131	131
Overall Study NOT COMPLETED	11	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Zoledronic Acid Plus Teriparatide Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Overall Study Adverse Event	5	2	3
Overall Study Withdrawal by Subject	3	1	2
Overall Study Lost to Follow-up	2	1	2
Overall Study Death	0	1	0
Overall Study Protocol Violation	0	1	0
Overall Study Administrative problems	1	0	0

Baseline Characteristics

Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zoledronic Acid Plus Teriparatide n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=138 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Total n=412 Participants Total of all reporting groups
Age Continuous	65.0 years STANDARD_DEVIATION 8.78 • n=5 Participants	66.1 years STANDARD_DEVIATION 9.02 • n=7 Participants	63.8 years STANDARD_DEVIATION 9.08 • n=5 Participants	65.0 years STANDARD_DEVIATION 8.99 • n=4 Participants
Sex: Female, Male Female	137 Participants n=5 Participants	137 Participants n=7 Participants	138 Participants n=5 Participants	412 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: Baseline through Week 52

Population: The intent-to-treat (ITT) population consisted of all randomized patients with available data.

Outcome measures

Outcome measures
Measure	Zoledronic Acid Plus Teriparatide n=122 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=128 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=131 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52	7.51 Percent change Standard Error 0.414	4.37 Percent change Standard Error 0.401	7.05 Percent change Standard Error 0.398

SECONDARY outcome

Timeframe: Baseline through Week 13 and Week 26

Population: The intent-to-treat (ITT) population consisted of all randomized patients with available data. ITT patients with evaluable measurements at both baseline and post-baseline within each efficacy visit window were analyzed.

Outcome measures

Outcome measures
Measure	Zoledronic Acid Plus Teriparatide n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=138 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26 At Week 13 (n= 127, 131, 131)	4.65 Percent Change Standard Error 0.302	2.97 Percent Change Standard Error 0.297	2.88 Percent Change Standard Error 0.297
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26 At Week 26 (n= 128, 130, 132)	6.31 Percent Change Standard Error 0.337	3.87 Percent Change Standard Error 0.333	4.45 Percent Change Standard Error 0.330

SECONDARY outcome

Timeframe: Baseline through Week 13, Week 26 and Week 52

BMD measurements of the total hip by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.

Outcome measures

Outcome measures
Measure	Zoledronic Acid Plus Teriparatide n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=138 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52 At Week 13 (n= 127, 133, 133)	2.54 Percent Change Standard Error 0.222	1.53 Percent Change Standard Error 0.216	0.75 Percent Change Standard Error 0.216
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52 At Week 26 (n= 128, 130, 133)	2.31 Percent Change Standard Error 0.265	1.73 Percent Change Standard Error 0.262	0.89 Percent Change Standard Error 0.259
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52 At Week 52 (n= 123, 129, 129)	2.33 Percent Change Standard Error 0.312	2.16 Percent Change Standard Error 0.303	1.10 Percent Change Standard Error 0.304

SECONDARY outcome

Timeframe: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52

Population: The intent-to-treat (ITT) population consisted of all randomized patients with available data. n = ITT patients with a measurement at each visit, as determined by the efficacy visit window

Specialized tests for markers of bone formation such as n-terminal propeptide of type I collagen (P1NP) were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum P1NP was determined by the central laboratory.

Outcome measures

Outcome measures
Measure	Zoledronic Acid Plus Teriparatide n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=138 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Week 4 (n= 109, 110, 104)	61.74 ng/mL Standard Deviation 27.269	39.57 ng/mL Standard Deviation 20.532	93.63 ng/mL Standard Deviation 52.418
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Week 39 (n= 110, 115, 110)	97.00 ng/mL Standard Deviation 112.804	20.69 ng/mL Standard Deviation 13.326	153.92 ng/mL Standard Deviation 103.065
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Week 52 (n= 110, 113, 112)	112.87 ng/mL Standard Deviation 106.987	23.49 ng/mL Standard Deviation 16.137	137.53 ng/mL Standard Deviation 93.170
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Baseline (n= 126, 129, 121)	52.72 ng/mL Standard Deviation 24.815	53.64 ng/mL Standard Deviation 29.233	55.69 ng/mL Standard Deviation 28.631
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Week 8 (n= 106, 107, 98)	39.91 ng/mL Standard Deviation 22.412	21.68 ng/mL Standard Deviation 13.827	99.27 ng/mL Standard Deviation 48.404
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP) At Week 26 (n= 116, 119, 114)	65.26 ng/mL Standard Deviation 68.922	18.32 ng/mL Standard Deviation 15.255	156.97 ng/mL Standard Deviation 109.740

SECONDARY outcome

Timeframe: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52

Specialized tests for markers of bone formation such as β-CTx were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum β-CTx was determined by the central laboratory.

Outcome measures

Outcome measures
Measure	Zoledronic Acid Plus Teriparatide n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Zoledronic Acid n=137 Participants Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Placebo Zoledronic Acid Plus Teriparatide n=138 Participants Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Week 4 (n= 109, 110, 104)	0.05 ng/mL Standard Deviation 0.048	0.05 ng/mL Standard Deviation 0.059	0.45 ng/mL Standard Deviation 0.259
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Week 8 (n= 106, 107, 98)	0.09 ng/mL Standard Deviation 0.109	0.07 ng/mL Standard Deviation 0.112	0.60 ng/mL Standard Deviation 0.320
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Baseline (n= 126, 129, 121)	0.45 ng/mL Standard Deviation 0.191	0.44 ng/mL Standard Deviation 0.218	0.46 ng/mL Standard Deviation 0.222
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Week 26 (n= 116, 119, 114)	0.43 ng/mL Standard Deviation 0.419	0.12 ng/mL Standard Deviation 0.117	0.90 ng/mL Standard Deviation 0.537
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Week 39 (n= 110, 115, 110)	0.57 ng/mL Standard Deviation 0.525	0.15 ng/mL Standard Deviation 0.108	0.89 ng/mL Standard Deviation 0.503
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx) At Week 52 (n= 110, 113, 112)	0.64 ng/mL Standard Deviation 0.476	0.17 ng/mL Standard Deviation 0.122	0.83 ng/mL Standard Deviation 0.393

Adverse Events

Zoledronic Acid

Serious events: 20 serious events

Other events: 115 other events

Deaths: 0 deaths

Zoledronic Acid Plus Teriparatide

Serious events: 13 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo Zoledronic Acid Plus Teriparatide

Serious events: 15 serious events

Other events: 96 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Zoledronic Acid n=137 participants at risk Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion.	Zoledronic Acid Plus Teriparatide n=137 participants at risk Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.	Placebo Zoledronic Acid Plus Teriparatide n=137 participants at risk Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks.
Ear and labyrinth disorders Vertigo	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Gastrointestinal disorders Constipation	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	7.3% 10/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Gastrointestinal disorders Diarrhoea	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	8.0% 11/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Gastrointestinal disorders Dyspepsia	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Gastrointestinal disorders Nausea	10.9% 15/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	15.3% 21/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	13.9% 19/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Gastrointestinal disorders Vomiting	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	7.3% 10/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
General disorders Chills	9.5% 13/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	11.7% 16/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
General disorders Fatigue	12.4% 17/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	13.9% 19/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	9.5% 13/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
General disorders Influenza like illness	9.5% 13/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	14.6% 20/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
General disorders Oedema peripheral	8.0% 11/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
General disorders Pyrexia	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	12.4% 17/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.2% 3/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Bronchitis	12.4% 17/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Influenza	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Nasopharyngitis	11.7% 16/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	16.8% 23/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	14.6% 20/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Sinusitis	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	0.73% 1/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Upper respiratory tract infection	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Infections and infestations Urinary tract infection	9.5% 13/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Injury, poisoning and procedural complications Contusion	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Injury, poisoning and procedural complications Fall	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Arthralgia	21.9% 30/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	22.6% 31/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	13.1% 18/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Back pain	16.8% 23/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	16.8% 23/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	11.7% 16/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Bone pain	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	2.9% 4/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Myalgia	16.1% 22/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	10.9% 15/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.5% 2/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	10.9% 15/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	12.4% 17/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Nervous system disorders Dizziness	2.2% 3/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	3.6% 5/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.1% 7/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Nervous system disorders Headache	17.5% 24/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	17.5% 24/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	14.6% 20/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.
Vascular disorders Hypertension	4.4% 6/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	5.8% 8/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.	6.6% 9/137 • 52 weeks The safety population includes 411 patients, one less than the randomized population due to one patient who was randomized and never received any study medication.