Kidney DiseasePhase 1NCT00935831
Single Dose Safety Study for Compound to Treat Anemia in Patients With Renal Impairment
A Phase 1 study testing GSK1278863A in people with Kidney Disease, run by GlaxoSmithKline at 1 site in New Zealand.
Trial summary
The purpose of this study is to characterize the safety and tolerability of single doses of compound 1278863A in subjects with renal impairment. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Kidney Disease
- What is being tested?
- GSK1278863A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteNew Zealand
- Study dates
- 12 Aug 2009to 27 Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
- History of regular use of tobacco- or nicotine-containing in excess of 10 cigarettes per day or equivalent and an inability to abstain from tobacco or nicotine use from admission to the clinical research unit until discharge for each dosing period.
- Use of prescription medication known to be inhibitors of BCRP.
- Use of non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study drugs, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia. (if the clinical research unit uses heparin to maintain intravenous cannula patency)
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include cholecystectomy, gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue. Examples of conditions that could interfere with hepatic function include Gilberts syndrome.
- History of peptic ulcer disease.
- Subjects with polycystic kidney disease.
- Post-renal transplantation subjects.
- History of malignancy tumor. Non-melanoma skin cancer that has been definitely removed is allowed.
- Pregnant females as determined by positive serum Beta-hCG test at Screening or prior to dosing.
- Lactating females.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices of the prohibited fruits from 7 days prior to the first dose of study drug in Dosing Period 1 until the collection of the final pharmacokinetic blood sample in Dosing Period 2, unless in the opinion of the Investigator and Medical Monitor this will not interfere with the study procedures or compromise subject safety.
- The subject has participated in a clinical trial and has received an experimental investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four experimental investigational products within 12 months prior to the first dosing day.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single-Dose, Randomized and Single-Blind (Part 1), Fixed Sequence and Open-Label (Part 2), Studyto Evaluate the Safety, Pharmacokinetics, andPharmacodynamics of 1278863A in Subjects With RenalImpairment and Matched Healthy Volunteers
The purpose of this study is to characterize the safety and tolerability of single doses of compound 1278863A in subjects with renal impairment.
Read the detailed description
Compound 1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is being developed for the treatment of anemia. This study, PHI112843, will be the first administration of 1278863A to investigate the safety, tolerability, pharmacokinetics and/or pharmacodynamics of single oral doses of 50 mg and 150 mg in pre-dialysis subjects with moderate or severe renal impairment and 150 mg in hemodialysis-dependent subjects. Four to eight subjects will complete each dose cohort. Multiple blood samples for pharmacokinetic and/or pharmacodynamic analyses will be obtained post-dose in each cohort. Safety will be assessed by measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory safety tests.
- Conditions
- Kidney Disease
- Being tested
- GSK1278863A, Placebo
- Keywords
- Tolerability, Safety, Pharmacokinetics, Pharmacodynamics
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1278863ADrug
50mg, 150mg
PlaceboDrug
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: GSK1278863A |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC (0-24), Cmax, tmax and half-life
Measured: Parts 1&2: Days 1-3
Secondary outcomes (11)
Adverse Events reporting
Measured: throughout study
Safety Labs (Chemistry)
Measured: Screening, Day -1, 2, 3
Safety Labs (Hematology)
Measured: Screening, Days -1, 2, 3
Safety Labs (Urinalysis)
Measured: Screening, Days -1, 2, 3
Vital Signs (blood pressure and heart rate)
Measured: Screening, Days 1, 2, 3
12-lead ECG
Measured: Screening, Day 1
Clinical Monitoring/Observation
Measured: throughout
Actual values, rate of rise, rate of decline and maximum change from baseline in erythropoietin
Measured: Days 1, 2, 3
Actual values, rate of rise, rate of decline and maximum change from baseline in VEGF
Measured: Days 1, 2
Actual values, rate of rise, rate of decline and maximum change from baseline in Hepcidin
Measured: Days 1, 2
Actual values, rate of rise, rate of decline and maximum change from baseline in TIBC (total iron binding capacity)
Measured: Screening, Days 1, 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2009 (estimated)
- Study start12 Aug 2009
- Primary completion27 Apr 2010
- Study completion27 Apr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00935831
- Sponsor's protocol ID
- 112843
- Status last verified
- Jul 2017
- First submitted
- 7 Jul 2009
- Last updated
- 27 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-Dose, Randomized and Single-Blind (Part 1), Fixed Sequence and Open-Label (Part 2), Studyto Evaluate the Safety, Pharmacokinetics, andPharmacodynamics of 1278863A in Subjects With RenalImpairment and Matched Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00935831
- Acronym / sponsor ID
- 112843
- Conditions
- Kidney Disease
- Keywords
- Tolerability, Safety, Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2009 (actual)
- Primary completion
- 27 Apr 2010 (actual)
- Study completion
- 27 Apr 2010 (actual)
- First posted
- 9 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to characterize the safety and tolerability of single doses of compound 1278863A in subjects with renal impairment.
Detailed description
Compound 1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is being developed for the treatment of anemia. This study, PHI112843, will be the first administration of 1278863A to investigate the safety, tolerability, pharmacokinetics and/or pharmacodynamics of single oral doses of 50 mg and 150 mg in pre-dialysis subjects with moderate or severe renal impairment and 150 mg in hemodialysis-dependent subjects. Four to eight subjects will complete each dose cohort. Multiple blood samples for pharmacokinetic and/or pharmacodynamic analyses will be obtained post-dose in each cohort. Safety will be assessed by measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory safety tests.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Subjects with renal impairment, non-dialysis | Experimental | Drug: GSK1278863A, Drug: PlaceboSubjects 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. |
| Healthy volunteers | Experimental | Drug: GSK1278863A, Drug: PlaceboHealthy 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. |
| Hemodialysis dependent subjects | Experimental | Drug: GSK1278863AThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- A male or female is eligible to enroll and participate in this study if he/she:
- 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:
- 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.
Key exclusion criteria (33 listed)
- A hemoglobin value at Screening is:
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK1278863A50mg, 150mg | Drug | Healthy volunteers, Hemodialysis dependent subjects, Subjects with renal impairment, non-dialysis |
| Placebomatching placebo | Drug | Healthy volunteers, Subjects with renal impairment, non-dialysis |
Primary outcome
AUC (0-24), Cmax, tmax and half-life
Time frame: Parts 1&2: Days 1-3
11 secondary outcomes
Adverse Events reporting
Time frame: throughout study
Safety Labs (Chemistry)
Time frame: Screening, Day -1, 2, 3
Safety Labs (Hematology)
Time frame: Screening, Days -1, 2, 3
Safety Labs (Urinalysis)
Time frame: Screening, Days -1, 2, 3
Vital Signs (blood pressure and heart rate)
Time frame: Screening, Days 1, 2, 3
12-lead ECG
Time frame: Screening, Day 1
Clinical Monitoring/Observation
Time frame: throughout
Actual values, rate of rise, rate of decline and maximum change from baseline in erythropoietin
Time frame: Days 1, 2, 3
Actual values, rate of rise, rate of decline and maximum change from baseline in VEGF
Time frame: Days 1, 2
Actual values, rate of rise, rate of decline and maximum change from baseline in Hepcidin
Time frame: Days 1, 2
Actual values, rate of rise, rate of decline and maximum change from baseline in TIBC (total iron binding capacity)
Time frame: Screening, Days 1, 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2017.
- Results for study 112843 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1278863A in people with Kidney Disease, run by GlaxoSmithKline at 1 site in New Zealand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC (0-24), Cmax, tmax and half-life (time frame: Parts 1&2: Days 1-3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2017.