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Completed

NCT Number: NCT02010242

Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria

NADPH oxidase enzymes (NOX) have been implicated in the development of several diabetic complications including diabetic nephropathy. GKT137831 is the first in class NOX1/4 inhibitor.

The primary objective of this study is to evaluate the efficacy of oral GKT137831 in patients with residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.

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Key information

Conditions

Type 2 Diabetes Mellitus With Diabetic Nephropathy Albuminuria Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Male Urogenital Diseases Metabolic Diseases Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Proteinuria Signs and Symptoms Urination Disorders Urogenital Diseases Urologic Diseases Urological Manifestations

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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About this study

A double-blind, placebo-controlled, randomized, multicenter, parallel group Phase 2 study assessing a 12-week period of treatment with oral GKT137831 administered in addition to standard of care for patients with type 2 diabetes.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Male or female aged 18 to 80 years
  • History of type 2 diabetes, defined as fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or a glycated hemoglobin (HbA1c) >6.5% (48 mmol/mol) on at least 2 occasions prior to screening.
  • Albuminuria defined as a UACR of 300 to 3500 mg/g.
  • An eGFR ≥30 mL/min/1.73 m2, as calculated by the CKD-EPI formula.
  • Must be taking an ACEI or an ARB for at least 6 weeks prior to the first screening visit (Visit 1) and during the screening period. The dose must have been stable for at least 4 weeks prior to the first screening visit (Visit 1). Combination therapy associating an ACEI and an ARB is not permitted.

Key Exclusion Criteria:

  • History of type 1 diabetes
  • Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable.
  • Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study.
  • History of renal transplant or planned renal transplant during the study.
  • A history of acute renal dialysis or acute kidney injury (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] definition) within 12 weeks of the first screening visit (Visit 1)
  • HbA1c level >11% (97 mmol/mol).
  • History of hypothyroidism requiring hormone replacement therapy.
  • History of active cardiovascular disease
  • A personal or family history of long QT syndrome.
  • Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent

Treatment and study plan

GKT137831

Drug

1 capsule of 100 mg twice a day for the first 6 weeks of treatment, and 2 capsules of 100 mg twice a day for next 6 weeks of treatment

Placebo

Drug

1 capsule of Placebo, twice a day, oral treatment self-administered by the patient for the 12 weeks of treatment.

Primary outcomes

  1. Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group

    Time frame: Visit 4 (week -2) to visit 11 (week 12)

    UACR from baseline to Visits 9, 10, and 11 (i.e. weeks 8, 10 and 12 of the treatment period, respectively).

    Baseline for UACR is defined as the geometric mean of the geometric means of the UACR values measured on Day-14 (visit 4) and Day 1 (visit 5). End of treatment is defined as the geometric mean of the geometric means of the UACR values measured at week 8 (visit 9), week 10 (visit 10) and week 12 (visit 11).

Secondary outcomes

  1. Glucose Metabolism by Homeostatic Model Assessment (HOMA)

    Time frame: Visits 5 (week 0), 8 (week 6), and 11 (week 12)

    Change in homeostasis model assessment-estimated β cell function (HOMA-B) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) from baseline.

    HOMA-IR = fasting insulin (μIU/mL) x fasting glucose (mM/L)/22.5. A higher HOMA-IR value indicates greater insulin resistance.

    HOMA-B = 20 x fasting insulin (μIU/mL)/(fasting glucose [mmol/mL] - 3.5). Generally, a higher HOMA-B value indicates better beta-cell function, meaning the pancreas is producing insulin effectively.

  2. Glucose Metabolism HbA1c

    Time frame: Visit 5 (week 0), 8 (week 6) and 11 (week 12)

    Change in HbA1c from Baseline

  3. 24 Hours Albumin Excretion

    Time frame: Visits 5 (week 0) and 11 (week 12)

    Change in 24 hours Albumin excretion from baseline

  4. 24 Hours Urine UACR

    Time frame: Visits 5 (week 0) and 11 (week 12)

    Change in 24 hours Urine UACR from baseline

  5. eGFR Change by Study Visit

    Time frame: Visits 5 (week 0), 6 (week 2), 7 (week 4), 8 (week 6), 9 (week 8), 10 (week 10), 11 (week 12), follow up (week 16)

    Change in eGFR from baseline by study visit

Other outcomes

  1. Erectile Dysfunction

    Time frame: Visits 5 (week 0), and 11 (week 12)

    Changes at week 12 in IEFF questionnaire assessing erectile dysfunction in patients presenting with these diabetic complications at baseline (Baseline <=25 in the erectile function domain)- Score from 1 to 30. Score 1 to 10: severe erectile dysfunction, Score 11-16: moderate erectile dysfunction, Score 17-25: light erectile dysfunction, Score 26-30: normal erectile function

  2. Neuropathic Pain

    Time frame: Visits 5 (week 0), and 11 (week 12)

    Changes in Visual Analog Scale (VAS) assessing neuropathic leg pain in patients presenting with these diabetic complications at baseline (subjects with a baseline VAS>=20mm are included). A 100mm VAS scale was used with a range from 0-100mm where a higher score means worse pain. The presence of neuropathic pain is defined a VAS score of at least 20 mm.

Sponsors and collaborators

Lead sponsor

Calliditas Therapeutics AB

Industry

Registry information

Official study title

A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study Evaluating the Safety and Efficacy of Oral GKT137831 in Patients With Type 2 Diabetes and Albuminuria

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Dec 12, 2013
Registry last updated
Feb 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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