Clinical Trials Register

Summary
EudraCT Number:	2010-019439-37
Sponsor's Protocol Code Number:	M10-149
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:	2010-07-15
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

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-019439-37

A.3

Full title of the trial

A Phase 3, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Intact Parathyroid Hormone Levels in Pediatric Subjects Ages 10 to 16 years with Moderate to Severe Chronic Kidney Disease

A.3.1

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

Safety and Efficacy of Paricalcitol Capsules in decreasing serum parathyroid hormone levels in children 10-16 with Chronic Kidney Disease (CKD)

A.4.1

Sponsor's protocol code number

M10-149

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	AbbVie Deutschland 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	AbbVie Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd.
B.5.2	Functional name of contact point	euclinicaltrials@abbott.com
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park, Vanwall Road,
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628644475
B.5.5	Fax number	+441628644330
B.5.6	E-mail	euclinicaltrials@abbott.com

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	Yes
D.2.1.1.1	Trade name	Zemplar 1 microgram capsules, soft
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Capsule, soft
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	PARICALCITOL
D.3.9.1	CAS number	131918-61-1
D.3.9.2	Current sponsor code	ABT-358
D.3.9.3	Other descriptive name	(7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1α,3β,25-triol
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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, soft
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

Moderate to Severe Chronic Kidney Disease

E.1.1.1

Medical condition in easily understood language

Chronic Kidney Disease Stage 3 and 4

E.1.1.2

Therapeutic area

Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10064848
E.1.2	Term	Chronic kidney disease
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objectives of this study are as follows:
Part I: To determine the safety, tolerability, and pharmacokinetics of a single dose of 3 mcg paricalcitol capsules in pediatric subjects ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4).

Part II: To determine the safety and efficacy of paricalcitol capsules as compared to placebo in decreasing serum iPTH in pediatric subjects ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4) with 12 weeks double-blinded study drug and a minimum of 12 weeks open-label active drug.

E.2.2

Secondary objectives of the trial

To determine the safety and efficacy of paricalcitol capsules as compared to placebo in decreasing serum iPTH in pediatric subjects ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4) with 12 weeks double-blinded study drug and a minimum of 12 weeks open-label active drug.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects ≥ 10 years old and ≤ 16 years old.
2. Subject has voluntarily signed and dated an informed consent form and/or assent, or has had one signed by a parent or legal guardian, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject and/or parent or legal guardian has had the opportunity to ask questions. The informed consent must be signed prior to any study-specific procedures being performed.
3. Subject has CKD Stage 3 or 4 as determined by eGFR (15 to 59 mL/min/1.73 m2) at Screening.
4. Part II Subjects who have had a kidney or solid organ transplant ≥ 12 months prior to entry into the Treatment Phase with a stable, therapeutic calcineurin inhibitor drug level (at least two stable levels prior to enrollment into Part II of the study).
5. Subject has 25-hydroxyvitamin D levels ≥ 30 ng/mL at Screening (Part II Only).
6. Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator).
7. If taking phosphate binders, the subject has been on a stable dose (same type and regimen) for at least 4 weeks prior to the Screening Phase.
8. If receiving growth hormone, subject must be receiving it for > 3 months prior to the Screening Phase and expected to continue to receive it throughout the Treatment Phase.
9. All female subjects must have a negative pregnancy test prior to Treatment.
10. Female subjects must not be nursing, must use the following methods of contraception upon enrollment, and must continue to use these methods for the duration of the study:
● Double barrier method (any two of the following: condoms, contraceptive sponges, diaphragm, vaginal ring with spermicidal jellies or creams, or intrauterine device [IUD]).
● Hormonal contraceptives (oral, parenteral or transdermal) for 3 months prior to study drug administration.
● Females on stable (same dose and product for 3 months) estrogen or progestin therapy (not for contraception).
● Total abstinence from sexual intercourse during the study (minimum one complete menstrual cycle prior to study start).
11. To satisfy the Screening criteria (for subjects who are currently on a VDRA and need to complete a 2–4 week washout), the subject must have:
● eGFR between 15 to 59 mL/min/1.73 m2 (estimate by the Schwartz formula as outlined in Section 5.3.1.2).
● iPTH measurement that is ≥ 60 pg/mL (Stage 3 subjects) or ≥ 90 pg/mL (Stage 4 subjects).
● An adjusted serum calcium value ≥ 8.2 mg/dL (2.05 mmol/L) to ≤ 10.5 mg/dL (2.63 mmol/L).
● A serum phosphorus value ≥ 2.0 mg/dL (0.65 mmol/L) to ≤ 6.0 mg/dL (1.94 mmol/L).
12. For entry into the Treatment Phase (VDRA naïve subjects and those who have completed a 2–4 week washout), the subject must have:
● iPTH measurement that is ≥ 75 pg/mL (Stage 3 subjects) or ≥ 110 pg/mL (Stage 4 subjects).
● An adjusted serum calcium value ≥ 8.4 mg/dL (2.10 mmol/L) to ≤ 10.2 mg/dL (2.55 mmol/L).
● A serum phosphorus value ≥ 2.5 mg/dL (0.81 mmol/L) to ≤ 5.8 mg/dL (1.87 mmol/L).
● Must have Vitamin 25D level that is ≥ 30 ng/mL (Part II Only).

E.4

Principal exclusion criteria

1. Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.
2. Part I Subjects: All transplants except bone marrow transplant recipients (off immunosuppressant therapy).
3. Subjects who have had a small bowel transplant.
4. Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine).
5. Subject has had symptomatic or significant hypocalcemia requiring active Vitamin D therapy (i.e., calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase.
6. Subject has a history of active kidney stones (6 months prior to screening).
7. Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption.
8. Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet,
glucocorticoids in an equivalent dose of > 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to Treatment.
9. Subject is taking phosphate supplements.
10. Subject has a current malignancy (except for basal/squamous cell carcinoma) or clinically significant liver disease, in the opinion of the investigator.
11. Subject weighs < 25 kg (55 lbs.).
12. Subject has a history of illicit drug and/or alcohol abuse within 6 months prior to the Screening Phase or a positive urine drug test at Screening. Positive urine drug tests at screening which are due to controlled drugs prescribed for a medical need are not exclusionary.
13. Subject has evidence of poor compliance with diet or medication that may interfere, in the investigator's opinion, with adherence to the protocol.
14. Subject has received any investigational drug within 4 weeks prior to the Screening Phase.
15. Subject is known to be HIV positive.
16. For any reason, subject is considered by the investigator to be an unsuitable candidate (i.e., unable to swallow capsules, lack of a telephone) to receive paricalcitol capsules or is put at risk by the study procedures.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of subjects who achieve two consecutive ≥ 30% reductions from baseline in iPTH levels during the 12-week double-blind portion of the study regardless of CKD stage.

The primary safety variable is the incidence of clinically meaningful hypercalcemia (2 consecutive serum calcium values > 10.2 mg/dL [2.55 mmol/L]).

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy endpoint evaluated at 12 weeks. Safety assessments will be evaluated throughout the study, including Follow-Up.

E.5.2

Secondary end point(s)

Secondary efficacy variables include:
1. The proportion of subjects who achieve a final iPTH value within K/DOQI iPTH target ranges (Table 6) will be evaluated within each CKD stage.
2. The mean change in iPTH from baseline to each post baseline visit (Weeks 2, 4, 8 and 12).
3. The proportion of subjects who achieve a final value within the applicable K/DOQI target ranges for calcium and for phosphorus. K/DOQI recommends serum calcium is maintained within age appropriate normal ranges and serum phosphorus is maintained at or above the age appropriate lower limits and no higher than the age appropriate upper limits.
4. The mean change in FMV UACR from baseline to each post baseline visit (Weeks 4, 8 and 12).

The following safety evaluations will be performed during the PK study: adverse event monitoring and vital signs, physical examinations, ECGs and laboratory tests assessments. In Part II safety will also be assessed through SAE and adverse event monitoring, changes from baseline in chemistry, hematology and urinary laboratory variables, changes from baseline in vital signs and physical examinations and progressive changes in kidney function observed via changes in eGFR in conjunction with cystatin C levels and subjects requiring dialysis.

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy endpoints evaluated at weeks 2, 4, 8 and 12. Safety assessments will be evaluated throughout the study, including Follow-Up.

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

Yes

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

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

12 week double-blinded followed by 12 week open label

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Germany

Portugal

Singapore

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

The end-of-study is defined as the date of the last subject's 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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1