Primary Objective: To evaluate the safety and tolerability of Hectorol Capsules during 52 weeks of treatment in patients with Stage 3 or Stage 4 CKDSecondary Objective: To evaluate the efficacy of Hectorol Capsules during 52 weeks of treatment in…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety Endpoints:
• Incidence of adverse events and serious adverse events.
• Changes in physical examination findings, vital signs, or laboratory
evaluations.
Efficacy Endpoint:
The efficacy endpoint will be the proportion of patients meeting the iPTH
target range (defined as iPTH less than or equal to 70 pg/mL (7.7 pmol/L) for
Stage 3 patients and iPTH less than or equal to 110 pg/mL (12.1 pmol/L) for
Stage 4 patients) during the Treatment Period.
Secondary outcome
Not applicable.
Background summary
Hectorol has been marketed in the US since 1999 with no new safety concerns
being identified in CKD 3, 4 or 5 patients with any of the available
formulations.
However there remains limited data on long term safety. To date, clinical
trials with Hectorol have treated patients up to 24 weeks5. This open-label,
single-arm study will evaluate the safety and tolerability of Hectorol over a
52-week treatment period.
Study objective
Primary Objective: To evaluate the safety and tolerability of Hectorol
Capsules during 52 weeks of treatment in patients with Stage 3 or Stage 4 CKD
Secondary Objective: To evaluate the efficacy of Hectorol Capsules during 52
weeks of treatment in patients with Stage 3 or Stage 4 CKD.
Study design
This is a Phase 3, multicenter, open-label study in patients with Stage 3 or 4
CKD. The study consists of a washout Period of u to 5 weeks duration followed
by a 52-weeks treatment period.
Schematic
Period: (Washout Period) (-------------Treatment
Period-------------------------------)
[---------------------]X[-------------------------------------------------------
-----------]
Week: Screening -1 0 2 4 6 8 10 12 16 20
24 28 36 44 52
Enroll
Washout Period
At Screening, the study will be described to the patient and a signed Informed
Consent will be obtained. The eligibility criteria will be reviewed.
All patients will be assessed for medical history and concomitant medications.
A physical examination will be performed and vital signs will be measured. The
following laboratory assessments will be performed: serum pregnancy (if
applicable), serum chemistry profile, hematology, urinalysis, intact
parathyroid hormone (iPTH), corrected serum calcium, phosphorus, albumin,
calcium x phosphorus product (CaxP), and estimated glomerular filtration rate
(GFR).
Patients taking active vitamin D (alfacalcidiol, calcitriol, or paricalcitol)
or calcimimetic therapy will be instructed to discontinue this therapy and the
Week-1 will be scheduled in 28 to 35 days.
Patients not prescribed an active vitamin D therapy or calcimimetic and
currently on a stable renal diet and/or phosphate binder therapy (if needed)
will be asked to return for Week -1 Visit 7 (+/- 5days) days later.
At the Week -1 visit, all subjects must be washed out of any active vitamin D
or calcimimetic therapy for at minimum 28 days. The subject*s eligibility
criteria will be confirmed. The following laboratory assessments will be
performed: iPTH, corrected serum calcium, phosphorus, albumin, calcium x
phosphorus product, spot urine calcium/creatinine ratio and spot urine
protein/creatinine ratio.
Treatment Period
At Week 0, eligible patients will be enrolled. A physical examination will be
performed and vital signs will be collected. The following laboratory
assessments will be performed at the baseline Week 0 Visit: serum pregnancy (if
applicable), serum chemistry profile, hematology, urinalysis, iPTH, corrected
serum calcium, phosphorus, albumin, CaxP and a storage sample will be collected.
During the following 52-week Treatment Period study visits will occur every two
weeks for the first 12 weeks, then monthly until week 28 and bi-monthly
thereafter.
Patients will be dispensed study drug and asked to consume the assigned
doxercalciferol dose daily. The dose of study drug will be titrated as
necessary to maintain the iPTH level within the K/DOQI target range: for Stage
3 patients, 35-70 pg/mL (3.85 - 7.7 pmol/L); for Stage 4 patients, 70-110 pg/mL
(7.7 - 12.1 pmol/L).
At all Treatment Period Visits the following blood analyses will be conducted:
iPTH, corrected serum calcium, phosphorus, albumin, and CaP. Additionally at
Weeks 24 serum pregnancy (if applicable), serum chemistry profile, hematology,
and urinalysis panel will be conducted. At Week 52 or the Early Termination
Visit, the following additional laboratory assessments will be performed: serum
pregnancy (if applicable), serum chemistry profile, hematology, urinalysis. A
physical examination will be performed and vital signs will be collected.
Adverse events (AEs) and concomitant medications will be collected from the
time of Informed Consent through week 52. Any SAE regardless of relationship to
treatment, occuring within 30 days of study completion or termination will be
collected.
Dose/route/regimen: see protocol summary (page 6 of the protocol).
Intervention
Ongcontrolled open-label study: all participating patients receive
doxercalciferol.
Study burden and risks
If a patient is treated for secundary hyperparathyroidism at the moment the
investigator does inform the patient about the study, there is a possible need
for a wash-out period of 5 weeks maximum to be able to participate in the study.
Altough washout periods of up to 8 weeks have been safely employed in many
similar studies without any observed harmful effects, a wash-out period is a
potential risk.
Doxercalciferol may be less effective and/or may be less tolerated or there may
be an increased risk of side effects than the patient's treatment before the
wash-out period.
Doxercalciferol may cause all, some or none of the side effects described
below. In addition, there is always a risk of side effects occurring which are
unusual or which are currently unknown.
The most important side effects (harmful effects) of doxercalciferol can be
calcium and/or phosphate levels in the blood which are too high or a
parathyroid hormone level in the blood which is too low. Too much calcium in
the blood during a prolonged period of time may result in hardening of soft
tissues, including the heart and the arteries, and too much phosphate in the
blood during a prolonged period of time may make the symptoms of
hyperparathyroidism worse. If the parathyroid hormone level in the blood
continues to be too low, this may lead to adynamic bone disease.
In view of the way doxercalciferol works, the drug may not be used in
combination with drugs that contain magnesium or aluminium, like binders based
on magnesium or aluminium. If you are using these drugs, you will be asked to
stop using them during the clinical study.
The risks associated with blood withdrawal from a vein in your arm are pain,
bruising and, in rare cases, infection at the injection site in your arm. Some
people may experience a slight light-headedness, nausea or fainting.
Gooimeer 10
1411 DD Naarden
Nederland
Gooimeer 10
1411 DD Naarden
Nederland
Listed location countries
Age
Inclusion criteria
1. Male or female, aged 18 years or older.
2. CKD Stage 3 or 4, defined as GFR from the abbreviated Modification of Diet in Renal Disease (MDRD) equation between 30 and 59 mL/min/1.73m2 for CKD Stage 3 or between 15 and 29 mL/min/1.73m2 for CKD Stage 4 at the Screening Visit
3. iPTH > 70 pg/mL (7.7 pmol/L) for CKD Stage 3 patients or > 110 pg/mL (12.1 pmol/L) for CKD Stage 4 patients but < 700 pg/mL (77 pmol/L) at Week -1.
4. In the opinion of the Investigator, the patient is willing and able to maintain compliance with phosphate binder therapy (if applicable) throughout the study duration.
5. Willing and able to stop any prior active vitamin D therapy (e.g. alfacalcidiol, calcitriol, or paricalcitol) and/or calcimimetic for 28 days prior to Week -1 and maintain this throughout the study.
6. Willing and able to sign and date an Informed Consent form unless the patient has a legally authorized representative. If the patient has a legally authorized representative, the legally authorized representative must sign and date the Informed Consent.
7. The patient, if of childbearing potential, must be willing to use an effective contraceptive method throughout the study, which includes barrier methods, hormones, or IUDs.
8. A level of understanding and willingness to cooperate with all visits and procedures as described by the study personnel.
Exclusion criteria
1. Corrected serum calcium > 10.0 mg/dL (2.5 mmol/L) at Week -1.
2. Serum phosphorus > 5.0 mg/dL (1.61 mmol/L) at Week -1.
3. In the opinion of the Investigator, the patient currently has poorly controlled diabetes mellitus, poorly controlled hypertension, active vasculitis, HIV infection, or any other clinically significant, unstable medical condition.
4. Abnormal liver function as measured by ALT/AST greater than three times the upper limit of normal (ULN) at the Screening Visit.
5. Deemed by the Investigator to have rapidly deteriorating renal function.
6. Spot urine calcium/creatinine ratio greater than 0.2 at Week -1.
7. Current malabsorption, severe chronic diarrhea, or ileostomy.
8. Any evidence of active malignancy except for basal cell carcinoma of the skin. A history of malignancy is not an exclusion.
9. Allergic reaction to a drug which, in the opinion of the Investigator, suggests an increased potential for hypersensitivity to a Vitamin D therapy.
10. Active ethanol or drug abuse, excluding tobacco use.
11. Current use of aluminum or magnesium based binders.
12. Pregnant or breast-feeding women.
13. Anticipated dialysis or planned renal transplant less than 12 months from Week 0.
14. Treatment with an investigational drug during 30 days preceding the start of screening.
15. Prior renal transplant
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001043-22-NL |
| CCMO | NL19634.068.07 |