Repeat Dose Safety and Efficacy Study for Compound to Treat Anemia

NCT01047397 | Completed Phase 2

• 2 other identifiers: 112844PHI112844
• Study Type: interventional
• Target: 107
• Locations: 4 countries
• Sites: 37

Brief Summary

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

Conditions

Kidney Disease

Keywords

hemodialysis; tolerability; pharmacokinetics; safety; anemia; renal impairment; repeat dose

Outcome Measures

Primary Outcomes (7)

• Rate of response for increase from baseline of hemoglobin levels

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

• Adverse Events reporting

  throughout study

• Safety Labs (Chemistry)

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

• Safety Labs (Hematology)

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

• Safety Labs (Urinalysis)

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

• Vital Signs (blood pressure and heart rate)

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

• ECG

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

Secondary Outcomes (5)

• AUC (0-∞), Cmax, tmax, t½

  Day 1, 15, 22

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

  Day 1, 15, 22, Folllow-up

• Actual values and change from baseline for VEGF, hepcidin, TIBC

  Day 1, 15, 22, Follow-up

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

  Screening, Day 1, 15, 29, 57

• Actual value and change from baseline for fetal hemoglobin

  Day 1, 29, 57

Study Arms (2)

Group 1

EXPERIMENTAL

Active Drug

Drug: 1278863A

Group 2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

1278863A DRUG

25mg, 50mg, 100mg

Group 1

Placebo DRUG

matching placebo

Group 2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• \. Has serum ferritin at Screening:
• ≥40 μg/L with the absence of microcytic or hypochromic RBCs (regardless of transferrin saturation %) OR
• μg/L with transferrin saturation % ≥20% (fraction saturation ≥0.20) and the absence of microcytic or hypochromic RBCs

You may not qualify if:

• 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.
• 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).
• \. 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (37)

GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

Location

GSK Investigational Site

Gosford, New South Wales, 2250, Australia

Location

GSK Investigational Site

St Leonards, New South Wales, 2065, Australia

Location

GSK Investigational Site

Herston, Queensland, 4029, Australia

Location

GSK Investigational Site

Box Hill, Victoria, 3128, Australia

Location

GSK Investigational Site

Reservoir, Victoria, 3073, Australia

Location

GSK Investigational Site

Bangalore, 560004, India

Location

GSK Investigational Site

Bangalore, 560017, India

Location

GSK Investigational Site

Hyderabad, 5000068, India

Location

GSK Investigational Site

Hyderabad, 500012, India

Location

GSK Investigational Site

Kalapet Pondicherry, 605014, India

Location

GSK Investigational Site

Mumbai, 400008, India

Location

GSK Investigational Site

New Delhi, India

Location

GSK Investigational Site

Visakhapatnam, 530002, India

Location

GSK Investigational Site

Auckland, 1150, New Zealand

Location

GSK Investigational Site

Christchurch, 8140, New Zealand

Location

GSK Investigational Site

Moscow, 109240, Russia

Location

GSK Investigational Site

Moscow, 109472, Russia

Location

GSK Investigational Site

Moscow, 115093, Russia

Location

GSK Investigational Site

Moscow, 119021, Russia

Location

GSK Investigational Site

Moscow, 119620, Russia

Location

GSK Investigational Site

Moscow, 123183, Russia

Location

GSK Investigational Site

Moscow, 125101, Russia

Location

GSK Investigational Site

Nizhny Novgorod, 603032, Russia

Location

GSK Investigational Site

Perm, 614097, Russia

Location

GSK Investigational Site

Saint Petersburg, 191015, Russia

Location

GSK Investigational Site

Saint Petersburg, 191104, Russia

Location

GSK Investigational Site

Saint Petersburg, 191186, Russia

Location

GSK Investigational Site

Saint Petersburg, 195067, Russia

Location

GSK Investigational Site

Saint Petersburg, 196247, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Saint Petersburg, 197110, Russia

Location

GSK Investigational Site

Saratov, 410053, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Volzhsky, 404120, Russia

Location

GSK Investigational Site

Yaroslavl, 150062, Russia

Location

GSK Investigational Site

Yekaterinburg, 620102, Russia

Location

Related Publications (1)

• 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.

  PMID: 36005278 DERIVED

MeSH Terms

Conditions

Kidney Diseases; Anemia; Renal Insufficiency

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: November 11, 2013

Record last verified: 2013-07

Locations

RU (21); AU (6); IN (8); NZ (2)