Trial Outcomes & Findings for A Study of Bonviva (Ibandronate) Once Monthly in Post-Menopausal Women With Osteopenia (NCT NCT00129623)

Last Updated: 2016-01-11

Results Overview

BMD was measured by a single dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine at the time of screening and at Month 12. A BMD measurement was considered unsuitable in case of detection of a fracture, an osteoarthritic process, or a scanning artifact that could not be removed to such a degree that accurate measurement of BMD would be considered jeopardized by the central reading center. The change in BMD was defined as the relative difference between the last individual measurement available at 12 months and Baseline, using the following formula: Relative change = 100 x (BMD at 1 year - BMD at baseline) / (BMD at baseline)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

160 participants

Primary outcome timeframe

Baseline and Month 12

Results posted on

2016-01-11

Participant Flow

This study was conducted at 10 centers in the United States.

Of the 451 participants who were screened, 160 participants were randomly assigned to the two treatment arms (Placebo and Ibandronate). The major reason for screening failure was participants did not meet the Bone Mineral Density (BMD) entry criteria.

Participant milestones

Participant milestones
Measure	Placebo Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Overall Study STARTED	83	77
Overall Study Intent-to-treat (ITT)/ Safety Population	83	77
Overall Study COMPLETED	73	65
Overall Study NOT COMPLETED	10	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Overall Study Adverse Event	3	7
Overall Study Refused Treatment	5	3
Overall Study Failure to Return	1	1
Overall Study Relocated job out of state	1	0
Overall Study Uncertainty to return	0	1

Baseline Characteristics

A Study of Bonviva (Ibandronate) Once Monthly in Post-Menopausal Women With Osteopenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Total n=160 Participants Total of all reporting groups
Age, Continuous	53.4 years STANDARD_DEVIATION 3.83 • n=93 Participants	53.7 years STANDARD_DEVIATION 3.64 • n=4 Participants	53.5 years STANDARD_DEVIATION 3.73 • n=27 Participants
Sex: Female, Male Female	83 Participants n=93 Participants	77 Participants n=4 Participants	160 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=68 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Relative Change From Baseline in Mean Bone Mineral Density (BMD) of the Lumbar Spine (L2 to L4) at Month 12	-0.3941 Percentage Standard Error 0.4148	3.7285 Percentage Standard Error 0.4229

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point.

BMD was measured by a single dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine at the time of screening and at Month 12. A BMD measurement was considered unsuitable in case of detection of a fracture, an osteoarthritic process, or a scanning artifact that could not be removed to such a degree that accurate measurement of BMD would be considered jeopardized by the central reading center. The absolute change from Baseline in mean BMD of the lumbar spine (L2-L4) was measured as g/cm\^2 and summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=68 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Absolute Change From Baseline in Mean Lumbar Spine BMD at Month 12	-0.0039 g/cm^2 Standard Deviation 0.0319	0.0322 g/cm^2 Standard Deviation 0.0315

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point.

BMD was measured by a single DEXA scan of the proximal femur at the time of screening and at Month 12. The relative (%) change from Baseline in BMD of the proximal femur (total hip, trochanter, femoral neck) at Month 12 was summarized using descriptive statistics. BMD of fractured bones that could impact the scan area were not taken into account.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=68 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Relative Change From Baseline in Mean Proximal Femur BMD at Month 12 Total hip	-0.9265 Percentage Standard Deviation 1.8790	1.4855 Percentage Standard Deviation 2.1862
Relative Change From Baseline in Mean Proximal Femur BMD at Month 12 Trochanter	-0.9120 Percentage Standard Deviation 3.0025	2.8688 Percentage Standard Deviation 3.0906
Relative Change From Baseline in Mean Proximal Femur BMD at Month 12 Femoral Neck	-0.7537 Percentage Standard Deviation 3.7743	1.0930 Percentage Standard Deviation 2.6466

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point.

BMD was measured by a single DEXA scan of the proximal femur at the time of screening and at Month 12. The absolute change from baseline in BMD of the proximal femur (total hip, trochanter, femoral neck) at Month 12 was summarized using descriptive statistics. BMD of fractured bones that could impact the scan area were not taken into account.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=68 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Absolute Change From Baseline in BMD of the Proximal Femur at Month 12 Total hip	-0.0083 g/cm^2 Standard Deviation 0.0163	0.0133 g/cm^2 Standard Deviation 0.0194
Absolute Change From Baseline in BMD of the Proximal Femur at Month 12 Trochanter	-0.0061 g/cm^2 Standard Deviation 0.0185	0.0182 g/cm^2 Standard Deviation 0.0199
Absolute Change From Baseline in BMD of the Proximal Femur at Month 12 Femoral neck	-0.0061 g/cm^2 Standard Deviation 0.0284	0.0078 g/cm^2 Standard Deviation 0.0202

SECONDARY outcome

Timeframe: Baseline and 3, 6 and 12 months

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point. n = the number of participants analyzed at a given time point.

Fasting blood samples were collected from participants for analysis of serum CTX (sCTX), which is a biochemical marker of bone resorption. Relative change from baseline of sCTX after 3, 6, and 12 months of treatment was summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Relative Change From Baseline in Serum C-telopeptide Crosslinks of Type 1 Collagen (CTX) Month 3, n = 81, 72	-4.2230 Percentage Interval -11.4068 to 2.2989	-55.7688 Percentage Interval -61.9565 to -46.7669
Relative Change From Baseline in Serum C-telopeptide Crosslinks of Type 1 Collagen (CTX) Month 6, n = 77, 72	-6.5934 Percentage Interval -14.359 to 0.6658	-61.6459 Percentage Interval -64.5652 to -52.3364
Relative Change From Baseline in Serum C-telopeptide Crosslinks of Type 1 Collagen (CTX) Month 12, n = 75, 68	-6.7416 Percentage Interval -14.6388 to 5.9238	-56.5432 Percentage Interval -61.8357 to -46.7836

SECONDARY outcome

Timeframe: Baseline and 3, 6, 12 months

Fasting blood samples were collected from participants for analysis of sCTX, which is a biochemical marker of bone resorption. Absolute change from baseline of sCTX after 3, 6, and 12 months of treatment was summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Absolute Change From Baseline in sCTX Month 3, n = 81, 72	-0.0350 ng/ml Interval -0.062 to 0.013	-0.2570 ng/ml Interval -0.293 to -0.206
Absolute Change From Baseline in sCTX Month 6, n = 77, 72	-0.0350 ng/ml Interval -0.067 to 0.005	-0.2675 ng/ml Interval -0.309 to -0.23
Absolute Change From Baseline in sCTX Month 12, n = 75, 68	-0.0320 ng/ml Interval -0.089 to 0.025	-0.2560 ng/ml Interval -0.303 to -0.185

SECONDARY outcome

Timeframe: Up to 12 months

Population: The ITT population included participants who were randomized, received at least one dose of the trial medication and had baseline and at least one follow-up evaluation data point.

Percent responders were defined as follows: Participants with a) lumbar spine (LS) BMD, equal to or above Baseline at Month 12 b) proximal femur BMD, equal to or above Baseline at Month 12 c) Both lumbar spine and proximal femur BMD, equal or above Baseline at Month 12. BMD of the lumbar spine was defined as the BMD of at least two vertebrae (L2-L4) that were not fractured and not affected by an osteoarthritic process, or a scanning artifact that could not be removed to such a degree that accurate measurement of BMD would be considered jeopardized by the central reading center. Proximal femur included total hip, trochanter and femoral neck sites.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Percentage of Responders Lumbar spine equal to or above baseline	38.6 Percentage	88.2 Percentage
Percentage of Responders Proximal femur equal to or above baseline	15.5 Percentage	60.3 Percentage
Percentage of Responders LS and proximal femur equal to or above baseline	8.5 Percentage	54.4 Percentage

SECONDARY outcome

Timeframe: Up to 15 days after end of study treatment (Approximately 2 years)

Population: The safety population included participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.

An AE is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	64 participants	60 participants
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) SAE	1 participants	3 participants

SECONDARY outcome

Timeframe: Screening up to 12 months

Population: The safety population included participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.

Blood for laboratory tests was taken at screening and immediately before participants received their monthly study medication at months 3, 6, and 12. The laboratory tests included: Hematology \[white blood cells (WBCs), platelets, hematocrit, and hemoglobin\] and Chemistry \[albumin, creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), total calcium, 25-hydroxy vitamin D, phosphate, magnesium, sodium, potassium, and chloride\].

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=77 Participants Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Number of Participants With Marked Laboratory Abnormalities WBC, low	1 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities ALT, high	2 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities Phosphate, high	1 participants	0 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Ibandronate (IBN) 150 mg Monthly

Serious events: 3 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=82 participants at risk；n=83 participants at risk Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=76 participants at risk；n=77 participants at risk Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Infections and infestations Cellulitis	1.2% 1/83 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	0.00% 0/77 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Infections and infestations Pyelonephritis	0.00% 0/83 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	1.3% 1/77 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
General disorders Chest pain	0.00% 0/83 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	1.3% 1/77 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/83 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	1.3% 1/77 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=82 participants at risk；n=83 participants at risk Participants with postmenopausal osteopenia were administered matching placebo tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg calcium and 400 international units \[IU\] vitamin D) once a day as dietary supplements for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.	Ibandronate (IBN) 150 mg Monthly n=76 participants at risk；n=77 participants at risk Participants with postmenopausal osteopenia were administered 150 mg Ibandronate (IBN) tablet orally once monthly. All participants received OSCAL tablet (containing 500 mg/d calcium and 400 international units \[IU\]/d vitamin D) once a day as dietary supplements, for the duration of the study. Participants received a total of 12 months of treatment and were followed for an additional period of 15 days.
Musculoskeletal and connective tissue disorders Arthralgia	9.8% 8/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	15.8% 12/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Musculoskeletal and connective tissue disorders Pain in extremity	6.1% 5/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	6.6% 5/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Musculoskeletal and connective tissue disorders Back pain	6.1% 5/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	2.6% 2/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Musculoskeletal and connective tissue disorders Myalgia	2.4% 2/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	6.6% 5/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Infections and infestations Upper respiratory tract infection	14.6% 12/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	7.9% 6/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Infections and infestations Nasopharyngitis	4.9% 4/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	3.9% 3/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Infections and infestations Urinary tract infection	7.3% 6/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	1.3% 1/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Gastrointestinal disorders Dyspepsia	4.9% 4/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Gastrointestinal disorders Nausea	3.7% 3/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	6.6% 5/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Gastrointestinal disorders Dental caries	3.7% 3/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Psychiatric disorders Depression	1.2% 1/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Psychiatric disorders Insomnia	1.2% 1/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Nervous system disorders Headache	4.9% 4/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
Metabolism and nutrition disorders Hypercholesterolaemia	1.2% 1/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.
General disorders Influenza like illness	0.00% 0/82 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.	5.3% 4/76 • Up to 15 days after end of study treatment (Approximately 2 years) SAEs and non-serious AEs were reported for members of the safety population, comprised of participants who had at least one dose of the trial medication documented in the CRF whether withdrawn prematurely or not.