Study of a new drug’s effect on anemia in subjects with impaired kidney function who are not on dialysis

• Conditions: Anemia associated with chronic kidney disease; MedDRA version: 14.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-004050-29-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-29
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria as
verified at Screening (Week -1):
1. Age and weight: >/= 18 years of age and >/= 45 kg.
2. Dialysis, rhEPO use and CKD:
a. Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or peritoneal dialysis) or dialysis planned during the time the subject would be enrolled in the study.
b. No current or prior rhEPO use within the past 7 weeks; e.g., epoetins (or their
biosimilars), darbepoetin, Mircera (methoxy polyethylene glycol epoetin beta), peginesatide or their biosimilars.
c. KDOQI CKD stages 3/4/5 defined by eGFR using the Modification of Diet for
Renal Disease (MDRD).
3. Lab inclusions
a. Hgb: Hgb concentrations 8.5-11.0 g/dL (inclusive) as outlined in Section 4.2.
b. Vitamin B12: Above the lower limit of the reference range (may rescreen in 2
months).
c. Folate: =2.0 ng/mL at Screening (may rescreen in a month).
d. Ferritin: =40 ng/mL with the absence of microcytic or hypochromic RBCs.
e. TSAT within the reference range.
4. Iron replacement therapy: Stable maintenance dose of oral iron replacement
therapy, if required, that will be maintained throughout the study. NOTE: IV iron
replacement therapy is not allowed the two weeks prior to Screening through the end
of the study (Week 6).
5. QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block
obtained at Screening Visit, based on Central Reader’s interpretation.
NOTE: Two additional ECGs are required if ECG interpretation indicates possible
prolonged QTc as defined by QTcB value on the initial tracing. The average of these three ECGs (based on the Central Reader’s interpretation) will be used to determine eligibility.
6. Females: Eligible to participate if she is:
a. Of childbearing potential, and must agree to use one of the approved contraception methods outlined in Section 6.3.5 from Screening until completion
of the Follow-up Visit OR
b. Of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation of hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)>40 MIU/ml and estradiol <40 pg/ml is confirmatory]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved
contraception methods if they wish to continue their HRT during the study.
Otherwise they must discontinue HRT to allow confirmation of post-menopausal
status prior to study enrollment. For most types of HRT, at least 2 weeks will
elapse between the cessation of therapy and the blood draw; this interval depends
on the type and dosage of HRT. Following confirmation of their postmenopausal
status, they can resume use of HRT during the study without use of a contraceptive method.
7. Males: Must agree to use one of the approved contraceptive methods as outlined in Section 6.3.5 from the time of Screening until completion of the Follow-up Visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

CKD-related criteria
1.Dialysis: Planning to initiate dialysis during the study or who have a high potential for initiating dialysis during study participation.
1.Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
2.Laboratory exclusions
a.Total CPK: >5x the upper limit of the reference range.
b.HIV: Positive HIV antibody. Cardiovascular disease-related criteria
3.Prior CV events
a.History of myocardial infarction or acute coronary syndrome within the prior 6 months.
b.History of stroke or transient ischemic attacks (TIAs) within the prior 6 months.
4.Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
5.Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, defined as DBP >100 mmHg or SBP>160 mmHg.
6.Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), or other thrombosis related condition, within the prior 6 months.
7.Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases).
Other disease-related criteria
8.Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).
9.Hematological disease: Any hematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia) or any other cause of anemia other than renal disease.
10.Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alkaline phosphatase, ALT or AST > 2.0 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
NOTE: Those Hepatitis C positive are eligible provided these laboratory exclusions are not met.
11.Major surgery: Within the prior 12 weeks or planned during the study.
12.Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study.
13.Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease or active GI bleeding within the prior 12 weeks.
14.Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening through Day 1 (randomization).
NOTE: IV antibiotics as prophylaxis are allowed.
15.Malignancy: History of malignancy within 5 years of Screening or are receiving treatment for cancer or those with a strong family history of cancer (e.g., familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated.
16.Hyperparathyroid

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified