Single Dose Safety Study for Compound to Treat Anemia in Patients With Renal Impairment

NCT00935831 | Completed Phase 1

• 1 other identifier: 112843
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the safety and tolerability of single doses of compound 1278863A in subjects with renal impairment.

Conditions

Kidney Disease

Keywords

Tolerability; Safety; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• AUC (0-24), Cmax, tmax and half-life

  Parts 1&2: Days 1-3

Secondary Outcomes (11)

• Adverse Events reporting

  throughout study

• Safety Labs (Chemistry)

  Screening, Day -1, 2, 3

• Safety Labs (Hematology)

  Screening, Days -1, 2, 3

• Safety Labs (Urinalysis)

  Screening, Days -1, 2, 3

• Vital Signs (blood pressure and heart rate)

  Screening, Days 1, 2, 3

Study Arms (3)

Subjects with renal impairment, non-dialysis

EXPERIMENTAL

Subjects with moderate to severe renal impairment equivalent to National Kidney Foundation Kidney Disease Outcomes Quality Initiative stage 3 and stage 4 who are not undergoing dialysis will be included. Subjects will receive single 50 mg and 150 mg oral doses of GSK1278863A across two dosing periods in a single-blind, randomized sequence. Doses of GSK1278863A will be given as 25 mg and 100 mg tablets, with matching placebo tablets to maintain treatment blinding.

Drug: GSK1278863A; Drug: Placebo

Healthy volunteers

EXPERIMENTAL

Healthy subjects will be matched to the moderate and severe renally impaired subjects for gender, age, and BMI. Subjects will receive single 50 mg and 150 mg oral doses of GSK1278863A across two dosing periods in a single-blind, randomized sequence. Doses of GSK1278863A will be given as 25 mg and 100 mg tablets, with matching placebo tablets to maintain treatment blinding.

Drug: GSK1278863A; Drug: Placebo

Hemodialysis dependent subjects

EXPERIMENTAL

The arm will consist of subjects with severe renal impairment (end-stage renal failure) who have been on stable hemodialysis treatment scheduled three times per week. Subjects will receive single oral doses of 150 mg GSK1278863A in each of 2 dosing periods in an open-label, fixed sequence. GSK1278863A will be administered just prior to receiving scheduled hemodialysis in Dosing Period 1. In Dosing Period 2, subjects will receive a single oral dose of GSK1278863 the morning after completion of a scheduled hemodialysis session.

Drug: GSK1278863A

Interventions

GSK1278863A DRUG

50mg, 150mg

Healthy volunteers; Hemodialysis dependent subjects; Subjects with renal impairment, non-dialysis

Placebo DRUG

matching placebo

Healthy volunteers; Subjects with renal impairment, non-dialysis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A male or female is eligible to enroll and participate in this study if he/she:
• (Part 1) has Moderate to Severe Renal Impairment (equivalent to NKF KDOQI Stage 3 or 4, not receiving dialysis) as determined by estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated MDRD equation, OR has Normal Renal Function determined by creatinine clearance (CLCR) via the Cockcroft-Gault equation, using serum creatinine and demographic data, obtained at Screening. Subjects with Normal Renal Function should have no greater than trace blood or protein on Screening urinalysis.
• (Part 2) has severe renal impairment (end-stage renal failure) and has been on stable hemodialysis treatment (three times weekly) for 3 months prior to Screening.
• otherwise healthy or considered clinically stable with respect to underlying renal impairment as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• has clinical laboratory test results that are considered clinically stable in the opinion of the Principal Investigator, especially if the clinical abnormality or laboratory parameter is deemed associated with the subject's underlying renal impairment. A normal subject with a clinical abnormality or laboratory parameters outside the reference range may be included only if the Investigator and the Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• \- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods described in the protocol 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 forms of HRT, at least 2-4 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 post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study drug until completion of the Follow-up visit.
• Body weight greater than or equal to 50 kg and BMI within the range 17 - 33 kg/m2 (inclusive).
• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block. These can be based on single ECG value or average of triplicate values obtained over brief recording period.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• A hemoglobin value at Screening is:
• Healthy male subjects or post-menopausal females: \> 16.5 g/dL
• Healthy female subjects: \> 15.5 g/dL
• Renally impaired male or female subjects: \<10 g/dL
• The values of hematological parameters at Screening, for healthy subjects only, are outside the reference range and clinically significant deemed by the Investigator and Medical Monitor
• The values of the following tests at Screening, for healthy subjects only, are:
• TIBC: outside the reference range
• Serum iron: outside the reference range
• Serum ferritin: outside the reference range
• Clinically significant abnormal CPK determined by the Investigator and Medical Monitor.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening.
• A positive test for HIV antibody.
• A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. A positive pre-study drug screen, for medications that are prescribed to a subject for pre-existing condition(s), may be allowed if in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of drug abuse or dependence within 6 months of the study.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Christchurch, 8011, New Zealand

Location

Related Links

• Results for study 112843 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2009
• First Posted: July 9, 2009
• Study Start: August 12, 2009
• Primary Completion: April 27, 2010
• Study Completion: April 27, 2010
• Last Updated: July 27, 2017

Record last verified: 2017-07

Locations

NZ (1)