Roche trials database

Protocol number:

ML19982

Title of Study:

A randomized open-label study to investigate the impact of Bone Marker Feedback at 3 months on adherence to monthly oral Bonviva in women with post-menopausal osteoporosis supported by a patient relationship program

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Product name:

ibandronate [Bonviva/Boniva]

Generic name:

ibandronate

Therapeutic area:

• Post-Menopausal Osteoporosis

Clinical study summary:

This was a randomized, prospective, open-label, multi-national, multi-center, two arm study involving post-menopausal women with osteoporosis who were either naïve to bisphosphonate treatment or the last bisphosphonate treatment was more than 6 months ago. Patients were randomized to one of two treatment arms, one to receive bone marker feedback and the other not to receive bone marker feedback. All patients received Bonviva/Boniva (ibandronate) 150 mg once a month for 6 months.

Study center(s):

55 centers in Hungary, Latvia, Poland, Romania, Russian Federation, Slovakia, Slovenia

Phase of development:

IV

Objectives:

The primary objective was to assess the impact of bone marker feedback (using serum CTX and communication of results on adherence to once monthly Bonviva/Boniva in women with postmenopausal osteoporosis supported by patient relationship program (PRP)

The secondary objectives were as follows:

• To evaluate the satisfaction of treatment with monthly Bonviva/Boniva for each study arm as well as the whole study population including analyses of different patient categories based on the baseline variables (age, previous osteoporosis treatment if any)
• To evaluate patient satisfaction with regimen (drug treatment and physician handling)
• To evaluate patient satisfaction with a method of assessment through biomarker quantification
• To evaluate physician satisfaction with a method of assessment through biomarker quantification
• To evaluate the effect of monthly Bonviva/Boniva on suppression of bone turnover markers
• To evaluate the impact of adherence to monthly Bonviva/Boniva on bone marker response
• To assess the safety of monthly Bonviva/Boniva
• To evaluate the impact of PRP on adherence to monthly Bonviva/Boniva intake

Methodology:

This was a randomized, prospective, open-label, multi-national, multi-center, two arm study involving post-menopausal women with osteoporosis who were either naïve to bisphosphonate treatment or the last bisphosphonate treatment was more than 6 month ago.
After signing the informed consent form, eligible patient were randomized to one of the two treatment arms and completed the baseline questionnaires. Patients administered the study treatment every month for 6 months. Patients were encouraged to take their study medication on regular intervals. In addition, patients were supported by the patient relationship program (PRP). Serum CTX testing was performed at baseline and at the final study visits. In the bone marker feedback arm, patients had additional CTX testing at the month 3 visit. Patients in both arms were given comparable adherence advice at month 3 as per good clinical practice. At the final visit at month 6, all patients were assessed for adherence and received an OPSAT-Q. Patients in the bone marker feedback arm had to complete the OPPS. In addition, at this visit all patients had to complete the Patient Relationship Program Satisfaction Exploratory Questionnaire (PRPSEQ). A telephone call was scheduled 15 to 30 days after the last study visit to collect additional safety information.

Number of patients (planned/analyzed):

716 patients randomized and treated

Diagnosis and main criteria for inclusion:

Ambulatory, post-menopausal women with osteoporosis; 55-85 years of age; eligible for bisphosphonate treatment; naive to bisphosphonate therapy, or lapsed users (last bisphosphonate intake ≥ 6 months ago).

Test product, dose and mode of administration or test procedure:

Ibandronate 150mg once a month

Duration of treatment:

6 months

Reference therapy, dose and mode of administration or reference procedure:

N/A

Criteria for evaluation (efficacy, safety):

Efficacy

Primary: Assessment of adherence

Secondary: Assessment of satisfaction, biochemical marker of bone turnover,

Safety: Adverse events, laboratory parameters, vital signs

Statistical methods:

Analysis of the primary variable

The null hypothesis in the primary analysis was that the proportion of patients with more than 83% adherence in the bone marker feedback group is not different from that in the no bone marker feedback group. The alternative hypothesis is tested that the proportion of patients with more than 83% adherence in the bone marker feedback group was not equal to that in the no bone marker feedback group. A Cochran-Mantel-Haenszel (CMH) test was conducted with an overall alpha level of 0.05 and provided an assessment of the difference in adherence rates between the biofeedback and no biofeedback arms adjusted for the stratification factor. The primary analysis was conducted on the ITT population.

Analysis of secondary variables

The patient satisfaction (OSAT-Q and OPPS) between the two treatment arms was compared using a GLM methodology. The ANOVA model included the treatment experience score as the response variable and study arm as factor. Descriptive statistics was provided for the PRPSEQ, and the percent change from baseline in serum CTX.

Safety Analysis

All patients in the safety population who had at least one post-baseline safety assessment were included in the safety analysis. Safety data such as adverse events and concomitant medications were summarized in terms of frequency and proportion of patients. Laboratory data were summarized using descriptive statistics.

Summary (efficacy, safety, other results):

Efficacy

Primary variables:

Based on the analyses in the subgroup with evaluable CTX values feedback did not statistically significantly (p=0.5818) influence the adherence to treatment as categorized in patients taking at least 83% of their medication (“Yes” group) versus patients who took less than 83% of their medications (“No” group).

Secondary variables:

QPSAT-Q (Osteoporosis Patient Satisfaction Questionnaire): The composite satisfaction score is high both in the BioFeedback arm and the No-BioFeedback arm both arms, 87.72% and 87.62% respectively. The difference between the arms was not statistically significant.

OPPS (Osteoporosis Patient Perception Survey) and OMSQ (Osteoporosis Medical Care Satisfaction Questionnaire): The composite satisfaction score is high both in the BioFeedback arm and the No-BioFeedback arm, 74.9% and 72.2% respectively. The difference between the arms was statistically significant. In agreement with the OPSAT-Q questionnaire, the non-adherence to medication lowers the self-rated composite satisfaction score from 72.4% (when adherent) to 59.6% when not adherent.  

CTX values: Adherence to treatment did not significantly affect the percentage change in CTX. Within the group of patients that adhered to the medication the CTX values decreased statistically significantly, whereas in the group of patients that did not adhere to the medication intake, a statistically significant reduction was not found.

Patients who showed more than 45% reduction in CTX value from Visit 1 to Visit 3, were more satisfied with the treatment than patients which showed a reduction smaller than 45% in CTX.

Safety

711 patients were included in the safety analysis. A total of 507 adverse events occurred during the study. Most of them were mild and moderate. Thirteen serious adverse events were reported. The majority of them was not considered as related to the study medication. Two patients died. These two deaths were not considered as related to the study medication.

Conclusions:

In conclusion, BioFeedback clearly affected the composite satisfaction score, albeit in interaction with other factors. A direct effect of BioFeedback on adherence to treatment as defined here for the primary efficacy analysis could not be found, although within the BioFeedback arm a direct effect of the quality of the BioFeedback arm on medication intake could be established.

Date of report:

28.08.2008

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