AzTrials
AzTrials

Kidney DiseasePhase 2NCT01047397

Repeat Dose Safety and Efficacy Study for Compound to Treat Anemia

A Phase 2 study testing 1278863A in people with Kidney Disease, run by GlaxoSmithKline at 37 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to characterize the safety and efficacy of repeat doses of compound 1278863A in subjects with anemia. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Kidney Disease
What is being tested?
1278863A
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
107 participants
Where
37 sitesin 4 countries
Study dates
Mar 2010to Feb 2011
Phase
Phase 2
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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female between 18 and 85 years of age inclusive, at the time of signing the informed consent.
  • 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, and not expected to go on dialysis until ≥ 8 weeks after first administration of investigational product. Stage 5, non-dialysis patients with eGFR of 10 15 mL/min per 1.73 m2 will also be eligible for Part 1 on a case-by-case basis.
  • (Part 2) has Severe Renal Impairment and has been on stable hemodialysis treatment for 1 month prior to Screening (subjects with planned transition to hemodialysis) or 3 months prior to Screening (subjects emergently placed on hemodialysis). These subjects are equivalent to NKF KDOQI Stage 5.
  • otherwise healthy or considered clinically stable with respect to underlying renal impairment and with respect to underlying/chronic disease 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 patient's underlying renal impairment.
Show all 24Show fewer
  • Meets the following erythropoiesis stimulating agent (ESA) criteria:
  • The patient is ESA naïve OR
  • If the patient has a scheduled ESA interval which is ≤ 7 days, ESA treatment must be discontinued for at least 7 days OR
  • If the patient has a scheduled ESA interval which is > 7 days, ESA treatment must be discontinued for at least that scheduled interval length (eg discontinued ≥ 14 days for a scheduled 14 day ESA interval) AND The patient will not resume ESA treatment until completion of the Follow-up Visit (Day 57).
  • Has a hemoglobin value:
  • For ESA naïve patients: ≤11.0 g/dL
  • For patients receiving ongoing ESA treatment: ≤11.5 g/dL at Screening with a re check value of ≤11.0 g/dL after appropriate ESA discontinuation according to Inclusion 3 and prior to commencing study drug dosing.
  • 5. Has serum ferritin at Screening:
  • ≥40 μg/L with the absence of microcytic or hypochromic RBCs (regardless of transferrin saturation %) OR
  • 25-39 μg/L with transferrin saturation % ≥20% (fraction saturation ≥0.20) and the absence of microcytic or hypochromic RBCs
  • Has Vitamin B12 and folate above the lower limit of normal at Screening
  • A female patient is eligible to participate if she is:
  • of childbearing potential, and must agree to use one of the contraception methods in Section 8.1.1. This criterion must be followed from the time of Screening until completion of the Follow-up Visit (Day 57) OR
  • 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 in Section 8.1.1 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 patients must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the time of the first dose of study drug until completion of the Follow-up Visit (Day 57).
  • Body weight ≥ 45 kg
  • QTcB or QTcF < 450 msec; or QTc < 480 msec in patients with bundle branch block. These should be based on an average of triplicate values obtained at Screening.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months prior to Screening and one of the following:
  • evidence of autoimmune anemia
  • prior anti-viral therapy
  • evidence of liver damage
  • A positive test for HIV antibody.
  • A pre-study drug screen that is positive due to drug use not associated with a current medication prescription. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
Show all 41Show fewer
  • A value at Screening is greater than 1.5 times the upper limit of reference range for AST, ALT, or direct bilirubin.
  • Hemolysis/hemolytic anemia or active bleeding/blood loss
  • Androgen therapy within 8 weeks prior to first dose of study drug (Day 1).
  • Red blood cell transfusion within 90 days prior to first dose of study drug (Day 1).
  • 8. Iron replacement therapy:
  • Intravenous iron replacement therapy within 30 days prior to the first dose of study drug on Day 1 until completion of the Follow-up Visit (Day 57).
  • Oral iron replacement therapy started or discontinued within 30 days prior to Screening. (Patients currently receiving oral iron replacement therapy which was initiated at least 30 days prior to Screening, will be allowed to continue their oral iron replacement therapy during the study and should not discontinue the therapy until after completion of all study drug doses and Day 29 assessments.)
  • History of thrombosis defined as deep vein thrombosis, stroke, pulmonary embolism or other thrombosis related condition within 1 year prior to Screening.
  • Known active decompensated hyperparathyroidism or history of bone marrow fibrosis.
  • Systemic hematologic disease, including, but not limited to sickle cell disease, hemosiderosis, hemochromatosis, myelodysplastic syndrome, hematologic malignancy, myeloma
  • Post-renal transplantation patients with functioning transplant. (Failed transplant subjects back on hemodialysis are eligible).
  • Acute peptic ulcer disease or history of chronic rectal bleeding.
  • History of malignancy tumor within 5 years prior to Screening or are receiving medication for cancer. Non-melanoma skin cancer within the past 5 years that has been definitively removed is allowed.
  • Patients 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 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.
  • Active infection or acute inflammatory disease as determined by clinical assessment.
  • Class III heart failure with evidence of recent progression (worsening dyspnea, hospitalization within 2-3 months for symptoms, etc), or Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Uncontrolled hypertension (diastolic BP >100 mmHg or systolic BP >160 mmHg at Screening)
  • Myocardial infarction or acute coronary syndrome within 1 year prior to Screening.
  • History of seizure disorder.
  • Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy that is likely to require treatment (intraocular injections or laser photocoagulation) during the study.
  • Pregnant females as determined by positive serum or urine hCG test at Screening or prior to the first dose of study drug (Day 1).
  • Lactating females.
  • History of drug abuse or dependence within 6 months prior to Screening.
  • Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
  • Use of prescription drugs within 7 days prior to first dose of study drug (Day 1) until after completion of all study drug doses and Day 29 assessments:
  • which are know to be inhibitors of CYP 2C8 OR
  • which are known to be both CYP 2C8 and OATP1B1 substrates OR
  • which rely mainly on OATP1B1/1B3 for hepatic clearance as described in Section 9 of the protocol.
  • Use of prescription drugs within 14 days prior to first dose of study drug (Day 1) until completion of all study drug doses and Day 29 assessments, which are known to be inducers of CYP 2C8, as described in Section 9 of the protocol.
  • 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 (Day 1) through the Follow-up Visit (Day 57), unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise patient safety and GSK Medical Monitor concurs.
  • 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 GSK Medical Monitor, contraindicates their participation.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia. (if the clinical site uses heparin to maintain intravenous cannula patency)
  • The patient 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 dose of study drug (Day 1).
  • Patient is mentally or legally incapacitated.

Trial locations and contacts

37 sites in 4 countries.

37 sites in 4 countries

Russia21 sites

  • GSK Investigational Site

    Moscow, 109240

  • GSK Investigational Site

    Moscow, 109472

  • GSK Investigational Site

    Moscow, 115093

  • GSK Investigational Site

    Moscow, 119021

  • GSK Investigational Site

    Moscow, 119620

  • GSK Investigational Site

    Moscow, 123183

  • GSK Investigational Site

    Moscow, 125101

  • GSK Investigational Site

    Nizhny Novgorod, 603032

  • GSK Investigational Site

    Perm, 614097

  • GSK Investigational Site

    Saint Petersburg, 191015

  • GSK Investigational Site

    Saint Petersburg, 191104

  • GSK Investigational Site

    Saint Petersburg, 191186

  • GSK Investigational Site

    Saint Petersburg, 195067

  • GSK Investigational Site

    Saint Petersburg, 196247

  • GSK Investigational Site

    Saint Petersburg, 197022

  • GSK Investigational Site

    Saint Petersburg, 197110

  • GSK Investigational Site

    Saratov, 410053

  • GSK Investigational Site

    Smolensk, 214006

  • GSK Investigational Site

    Volzhsky, 404120

  • GSK Investigational Site

    Yaroslavl, 150062

  • GSK Investigational Site

    Yekaterinburg, 620102

Other trials in Russia

India8 sites

  • GSK Investigational Site

    Bangalore, 560004

  • GSK Investigational Site

    Bangalore, 560017

  • GSK Investigational Site

    Hyderabad, 5000068

  • GSK Investigational Site

    Hyderabad, 500012

  • GSK Investigational Site

    Kalapet Pondicherry, 605014

  • GSK Investigational Site

    Mumbai, 400008

  • GSK Investigational Site

    New Delhi

  • GSK Investigational Site

    Visakhapatnam, 530002

Other trials in India

Australia6 sites

  • GSK Investigational Site

    Box Hill, Victoria, 3128

  • GSK Investigational Site

    Camperdown, New South Wales, 2050

  • GSK Investigational Site

    Gosford, New South Wales, 2250

  • GSK Investigational Site

    Herston, Queensland, 4029

  • GSK Investigational Site

    Reservoir, Victoria, 3073

  • GSK Investigational Site

    St Leonards, New South Wales, 2065

Other trials in Australia

New Zealand2 sites

  • GSK Investigational Site

    Auckland, 1150

  • GSK Investigational Site

    Christchurch, 8140

Other trials in New Zealand

About this study

Official title: A Phase IIa, Randomized, Single-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of 28-day Repeat Oral Doses of GSK1278863A in Anemic Pre-dialysis and Hemodialysis-dependent Patients

The purpose of this study is to characterize the safety and efficacy of repeat doses of compound 1278863A in subjects with anemia.

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, PHI112844, will be the first administration of compound 1278863A to investigate the pharmacodynamics/efficacy, safety, tolerability, and pharmacokinetics of repeat oral doses in anemic pre-dialysis patients with moderate or severe renal impairment and in hemodialysis-dependent patients.

Conditions
Kidney Disease
Being tested
1278863A, Placebo
Keywords
hemodialysis, tolerability, pharmacokinetics, safety, anemia, renal impairment, repeat dose
Medical subject headings
Kidney Diseases, Anemia, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 1278863ADrug

    25mg, 50mg, 100mg

  • PlaceboDrug

    matching placebo

Study groups in NCT01047397
Study groupRoleWhat they receive
Group 1ExperimentalActive Drug
Receives: Drug: 1278863A
Group 2Placebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of response for increase from baseline of hemoglobin levels

    Measured: Pre-dose, Day 1, Day 15, Day 22, Follow-up

  2. Adverse Events reporting

    Measured: throughout study

  3. Safety Labs (Chemistry)

    Measured: Screening, Day 1, 4, 8, 15, 22, 29, 36, 57

  4. Safety Labs (Hematology)

    Measured: Screening, Day 1, 4, 8, 15, 22, 29, 36, 57

  5. Safety Labs (Urinalysis)

    Measured: Screening, Day 1, 4, 8, 15, 22, 29, 36, 57

  6. Vital Signs (blood pressure and heart rate)

    Measured: Screening, Day 1, 4, 8, 15, 22, 29, 36, 57

  7. ECG

    Measured: Screening, Day 1, 4, 8, 15, 22, 29, 36, 57

Secondary outcomes (5)

  1. AUC (0-∞), Cmax, tmax, t½

    Measured: Day 1, 15, 22

  2. Actual values and change from baseline for erythropoietin, absolute and percent reticulocytes, hematocrit, and total RBCs

    Measured: Day 1, 15, 22, Folllow-up

  3. Actual values and change from baseline for VEGF, hepcidin, TIBC

    Measured: Day 1, 15, 22, Follow-up

  4. Actual values and change from baseline for transferrin saturation, serum iron, serum ferritin

    Measured: Screening, Day 1, 15, 29, 57

  5. Actual value and change from baseline for fetal hemoglobin

    Measured: Day 1, 29, 57

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01047397
Sponsor's protocol ID
112844
Other IDs
PHI112844
Status last verified
Jul 2013
First submitted
11 Jan 2010
Last updated
11 Nov 2013
Results posted
No
Data monitoring committee
No

Publications

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

    PubMed 36005278

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 1278863A in people with Kidney Disease, run by GlaxoSmithKline at 37 sites in 4 countries.

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 24 inclusion and 41 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 11 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Russia, India, Australia, 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Rate of response for increase from baseline of hemoglobin levels (time frame: Pre-dose, Day 1, Day 15, Day 22, Follow-up). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01047397, which also lists 1 linked publication.

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 11 Nov 2013; AzTrials last refreshed its copy on 30 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in