6520-9961-04

MEDICE Arzneimittel Pütter GmbH & Co. KG

Kuhloweg 37, Iserlohn, Germany, 58638

Medizinische Abteilung, MEDICE Arzneimittel Pütter GmbH & Co. KG, +49 2371937523, b.hellmann@medice.de

Medizinische Abteilung, MEDICE Arzneimittel Pütter GmbH & Co. KG, +49 2371937523, b.hellmann@medice.de

No

No

No

Final

09 Jul 2018

Yes

14 Mar 2017

Yes

14 Mar 2017

No

Nicotinamide MR compared to placebo as an add-on therapy to approved individual phosphate binders in the long term reduction of elevated phosphate levels in haemodialysis patients

The investigator should have discontinued the study medication for the following reasons: • Lack of efficacy of the study medication even after rescue therapies • Occurring of intolerable adverse effects even after dose reduction • Platelet count less than 75/nl • Creatine kinase increased ≥ 5 times the normal range • Transaminase (AST, ALT) increased ≥ 3 times the normal range • Use of medications/drugs not prescribed or allowed by the investigator and/or not permitted during the trial • Onset of pregnancy • Suspected relevant drug interaction(s) • Subsequent ascertainment of non-fulfilment of the inclusion criteria or fulfilment of the exclusion criteria • Continued trial participation unacceptable/unreasonable in the opinion of the investigator

15 Aug 2013

No

Yes

Poland: 133

Austria: 83

Germany: 507

723

723

0

0

0

0

0

0

507

216

0

Efficacy and Safety Evaluation (overall period)

Randomised - controlled

Placebo capulses were identical to verum. Labaratory measurement of serum nicotinamide and its metabolite concentrations were transfered to data management not before unblinding.

Yes

Nicotinamide MR 250 mg capsules

Capsule, hard

Oral use

Dosage was titrated depending on serum phosphate concentrations between 1 and 6 capsules per day. Once daily intake at bed time or twice daily intake after wakeup and at bedtime.

Placebo capsules

Capsule, hard

Oral use

Dosage was titrated depending on serum phosphate concentrations between 1 and 6 capsules per day. Once daily intake at bed time or twice daily intake after wakeup and at bedtime.

Efficacy and Safety Evaluation

Safety Population

The safety population includes all randomized patients who took the study medication at least once

Intention to Treat Population

Safety population with the exclusion of one legaly impaired patient.

Per Protocol Population

Patients of the Intention to treat with one of the following protocol deviations: • Lack of compliance (less than 75% or more than 125% of the prescribed daily dose either during the whole study or in 2 consecutive study visits [week 0 to week 12 or between week 8 and week 12]) • Study medication was temporarily withdrawn for > 14 days between week 0 and week 8 • Retrospectively identified violation of inclusion/exclusion criteria at screening • Incorrect study medication dispensed (randomization violated) • Unblinding • Confusion/mix up of provided study medication • Drop-out (study medication withdrawn or entire study stopped) before week 12

Completers population

All patients of the Per protocol population that neither terminated study medication intake permanently nor study participation prematurely (i.e. before week 52) and who had a record for serum phosphate at week 52 irrespective of whether the phosphate value at screening was missing.

Nicotinamide

Placebo

Safety Population

The safety population includes all randomized patients who took the study medication at least once

Intention to Treat Population

Safety population with the exclusion of one legaly impaired patient.

Per Protocol Population

Patients of the Intention to treat with one of the following protocol deviations: • Lack of compliance (less than 75% or more than 125% of the prescribed daily dose either during the whole study or in 2 consecutive study visits [week 0 to week 12 or between week 8 and week 12]) • Study medication was temporarily withdrawn for > 14 days between week 0 and week 8 • Retrospectively identified violation of inclusion/exclusion criteria at screening • Incorrect study medication dispensed (randomization violated) • Unblinding • Confusion/mix up of provided study medication • Drop-out (study medication withdrawn or entire study stopped) before week 12

Completers population

All patients of the Per protocol population that neither terminated study medication intake permanently nor study participation prematurely (i.e. before week 52) and who had a record for serum phosphate at week 52 irrespective of whether the phosphate value at screening was missing.

The primary criterion of this study was the serum phosphate concentration in mg/dL at W12 for the ITT population. The analysis was based on a linear mixed model to also address the stratification factors of the randomization. The factors/covariates study medication group, study site, individual additional phosphate binder (phosphate binder containing calcium, lanthanum carbonate and aluminum, and other phosphate binders) and initial value of phosphate (screening) were considered. The study medication group was included as a fixed effect; the study site was modelled as random effect (random intercept). The initial value of phosphate and the individual additional phosphate binder(s) were included as fixed effect covariates. Interactions were not considered in the primary model. The claim of superiority was based on a two-sided p-value related to the Wald-type test statistic for the treatment effect applying a two-sided significance concentration of 2.5%.

Primary

12 weeks

The analysis was based on a linear mixed model to also address the stratification factors of the randomization.

Nicotinamide v Placebo

673

Pre-specified

-0.506

2-sided

Secondary

12 weeks

Nicotinamide v Placebo

439

Pre-specified

-0.61

2-sided

The completers population consisted of patients who neither terminated study medication intake permanently nor study participation prematurely (i.e. before week 52) and who had a record for serum phosphate at week 52 irrespective of whether the phosphate value at screening was missing.

Secondary

52 weeks

Placebo v Nicotinamide

358

Post-hoc

From Screening examination until week 52. Adverse events occuring within 4 weeks after last intake of study medication were additionally recorded.

Adverse events were regristed continously during the clinical trial at each study visit. All adverse events were recorded irregardless wether the patient was under study medication or it was terminated.

16.1

Nicotinamide

Placebo