Clinical Trials Register

Summary
EudraCT Number:	2013-000488-95
Sponsor's Protocol Code Number:	6520-9961-04
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-07-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2013-000488-95

A.3

Full title of the trial

Efficacy and tolerability of nicotinamide as add-on therapy compared to placebo in dialysis-dependent patients with hyperphosphatemia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and tolerability of nicotinamide as add-on therapy compared to placebo in dialysis-dependent patients with elevated phosphat level

A.3.2

Name or abbreviated title of the trial where available

NOPHOS Trial

A.4.1

Sponsor's protocol code number

6520-9961-04

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	MEDICE Arzneimittel Pütter GmbH & Co. KG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MEDICE Arzneimittel Pütter GmbH & Co. KG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MEDICE Arzneimittel Pütter GmbH & Co. KG
B.5.2	Functional name of contact point	Medizinische Abteilung
B.5.3	Address:
B.5.3.1	Street Address	Kuhloweg 37
B.5.3.2	Town/ city	Iserlohn
B.5.3.3	Post code	58638
B.5.3.4	Country	Germany
B.5.4	Telephone number	+492371937512
B.5.5	Fax number	+4902371937360
B.5.6	E-mail	a.engels@medice.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Nicotinamid 250 mg retard Kapseln
D.3.4	Pharmaceutical form	Modified-release capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NICOTINAMIDE
D.3.9.1	CAS number	98-92-0
D.3.9.2	Current sponsor code	M111, nicotinamide MR
D.3.9.3	Other descriptive name	niacinamide, pyridine 3-carboxamide, pyridine 3-carboxylic acid amid, nicotinic acid amide, nicotinamide, vitamin PP
D.3.9.4	EV Substance Code	SUB09246MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Dialysis-dependent patients with hyperphosphatemia

E.1.1.1

Medical condition in easily understood language

Dialysis-dependent patients with elevated phosphat levels

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10020712
E.1.2	Term	Hyperphosphatemia
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Males or females aged 18 years or older
Patients with CKD stage 5 and on a stable haemodialysis regimen, 3 times a week for at least 6 months prior to screening
Dialysis sessions must be conducted either on Sunday, Monday (morning, midday/afternoon, evening or overnight) or on Tuesday (morning or midday/afternoon)
Dialysis regime must remain constant at least until visit W12
Unmodified phosphate binding therapy with one or two phosphate binders for at least 1 month prior to screening
Serum phosphate concentration at screening < 2.8 mmol/l (8,7 mg/dl) and > 1.45 mmol/l (4.5 mg/dl)
If the patient is on vitamin D replacement and/or active vitamin D therapy, the dose must have remained stable for at least 1 month prior to screening
If the patient takes calcimimetics, the dose must have remained stable for at least 1 month prior to screening

E.4

Principal exclusion criteria

Chronic heart failure NYHA III or IV in adequate volume state.
Cardiac decompensation, which required hospital admission in the last 6 months
Myocardial infarction in the last 3 months
Uncontrolled hypertension although receiving 3 or more antihypertensive medications
Patient with planned parathyroidectomy in the next year
High urgency transplant candidate as defined at Eurotransplant at screening
Peptic ulcers in the last 6 months
Gastro-intestinal hemorrhage - except anal skin tags - in the last 6 month
Patients with dysphagia or swallowing difficulties in the last 6 month
Intestinal obstructions / ileus in the last 6 month
Patients with impaired intestinal absorption (e.g. impaired intestinal motility, pseudo-obstructions, megacolon, short bowel syndrome, Crohn's or coeliac disease)
Active gastroparesis, identifiable from nausea and vomiting
Rhabdomyolysis
Severely impaired vision (e.g. macular edema, maculopathy, severe nonproliferative retinopathy or proliferative retinopathy)
Severe hepatic parenchymal diseases
Hypersensitivity to nicotinamide or one of the other ingredients
Absolute or severe lactose intolerance
Simultaneous participation in another clinical trial within the last 2 months
Patients who are legally incapacitated or are institutionalized by court or official order
Patient with an inadequate command, or no command of written and spoken national language
Failure to use highly-effective contraceptive methods in women of child-bearing age
Poorly controlled diabetes (HbA1c > 9%) at screening
Platelet count < 120/nl at screening
BMI < 19 at screening
Calcium > 2.65 mmol/l (10.6 mg/dl) at screening
Pathological creatine kinase value may not be ≥ 2 times the normal range (men > 380 U/l, women > 334 U/l) at screening;
Elevated transaminases (AST or ALT) more than 3 times the normal level at screening
Haemoglobin level < 8 g/dl at screening
Mean blood pressure of the last 6 measurement in the last 2 weeks prior screening > 180 mmHg systolic or > 110 mmHg diastolic.
Change of dialysis mode planned in the next year
Pregnant women or positive pregnancy test

E.5 End points

E.5.1

Primary end point(s)

Serum phosphate concentration

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks post baseline

E.5.2

Secondary end point(s)

Serum phosphate concentration: end value 24 and 52 weeks post baseline
Change from screening serum phosphate levels, end value 12, 24 and 52 weeks post baseline
Number of responders/non-responder of all randomized patients belonging to the ITT-population. Patients will be considered as non-responders, if the phosphate value is missing at the specific measurement time point (week 12, 24, and 52) or if the study medication was discontinued before the time point. For the remaining cases, a response is defined according to the following 4 definitions separately for each of the 3 measurement time points at week 12, 24 and 52:
1. serum phosphate concentration ≤ 1.78 mmol/l (5,5 mg/dl)
2. serum phosphate concentration ≤ 1.45 mmol/l (4.5 mg/dl)
3. Individual serum phosphate target range achieved
· (1.0 mmol/l (3.1 mg/dl) to 1.45 mmol/l (4.5 mg/dl) in patients with screening phosphate levels < 2.0 mmol/l (6.25 mg/dl)
· 1.0 mmol/l (3.1 mg/dl) to 1.78 mmol/l (5.5 mg/dl) in patients with screening phosphate levels ≥ 2.0 mmol/l (6.25 mg/dl
4. Individual serum phosphate concentration improved ≥ 0.2mmol/l (0.6 mg/dl) compared to screening
Number of responders applying the definition of responders above but limiting the analyses to patients under study medication at the end of the trial with no missing data at the concerning measurement time point.
Serum calcium concentration 12, 24 and 52 weeks post baseline
Intact parathormone (iPTH) 12, 24 and 52 weeks post baseline
High and low density lipoproteins (HDL, LDL) and triglycerides 12, 24 and 52 weeks post baseline
Number of patients receiving rescue therapy due to elevated serum phosphate

E.5.2.1

Timepoint(s) of evaluation of this end point

different time points (see secondary end points)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last subject last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

315

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

385

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

500

F.4.2

For a multinational trial

F.4.2.1

In the EEA

700

F.4.2.2

In the whole clinical trial

700

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

normal treatment of that condition

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-08-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-08-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-03-14

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials