A Study to Evaluate the Safety and Tolerability of ABT-614 and Its Effect on Kidney Function in Subjects With Type 2 Diabetes and Chronic Kidney Disease With Protein in Their Urine.

A Phase 1b, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Single-Dose of ABT-614 and the Effect of ABT-614 on Glomerular Filtration Rate in Subjects With Type 2 Diabetes and Chronic Kidney Disease With Albuminuria

To assess the safety, tolerability and pharmacokinetics of ABT-614 in subjects with type 2 diabetes and chronic kidney disease with albuminuria and to determine whether ABT-614 reduces glomerular filtration rate.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetics, Chronic Kidney Disease, Protein in Urine
• Intervention / Treatment: Drug: Placebo Comparator; Drug: ABT-614

Detailed Description

This Phase 1b, single-site, double-blind, randomized, placebo-controlled study will be conducted in three Periods; Baseline, Dosing and Outpatient. Eligible adult male and female subjects with type 2 diabetes and CKD (chronic kidney disease) with albuminuria will be selected to participate.

Eighteen subjects will be selected to participate in the Baseline Period to ensure that 16 subjects are enrolled in the Dosing Period. Subjects who are eligible from Screening will be confined to the study site beginning on Day -2 (the day before the Baseline Period infusion). On Day -1, subjects will be administered an iothalamate infusion to measure baseline GFR (glomerular filtration rate). Subjects who continue to be eligible on Day 1 will be randomized in a 1:1 ratio to receive either a 10 mg dose of ABT-614 or matching placebo daily, for 15 days.

On Day 15 subjects will be administered a second iothalamate infusion. Plasma and urine samples for ABT-614 and iothalamate will be collected. Subjects will be released from confinement on Day 20 after the completion of all study procedures including the 120-hour blood sample collection. Thereafter, subjects will return for outpatient visits on Days 25 and 30 as well as 30 days after the last dose of study drug. A ± 2 day window will be permitted on the 30-day Follow-up Visit to accommodate subject scheduling.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Site Reference ID/Investigator# 63442

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Male or female aged between 19 and 70 years, inclusive, at time of consent.
2. Type 2 diabetes receiving at least one anti-diabetic medication for at least one year at the time of Screening.
3. Hemoglobin A1c < 12% at the time of Screening.
4. Estimated glomerular filtration rate ≥ 30 mL/min calculated by the Cockcroft-Gault Formula at the time of Screening.
5. Urinary albumin to creatinine ratio 100 to 5000 mg/g creatinine at the time of Screening.

Exclusion Criteria

1. History of unusual or allergic reaction to iodine, to products containing iodine (for example., iodine containing foods) or to other radio-opaque agents.
2. Subject history of epileptic seizures or convulsions.
3. Clinically significant cardiac disease or family history of long-QT syndrome and/or subject and/or family history of unexplained, sudden cardiac death. History of myocardial infarction or coronary artery bypass graft is not exclusionary if occurrence is ≥ 12 months prior to the administration of study drug and the subject does not have conduction abnormality and has been stable without intervention, symptoms of ischemia or an increase in cardiovascular medications. Electrocardiography (ECG) should be compared with historical to ensure no new clinically significant changes have occurred.
4. History of gastric surgery, cholecystectomy, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, potential hydrogen (pH) or absorption.
5. Clinically significant respiratory (except mild asthma), gastrointestinal, hematologic, neurologic, thyroid or any uncontrolled medical illness or psychiatric disease or disorder.
6. Screening ECG with clinically significant abnormalities and/or confirmed Screening QTcF prolongation more than 430 milliseconds for males and 450 milliseconds for females or ECG with second or third degree atrioventricular block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator	Drug: Placebo Comparator; Placebo
Experimental: ABT-614	Drug: ABT-614; Active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in drug concentration	Blood and urine tests	Day -1 (Baseline) and up to Day 15
Change in glomerular filtration rate	Blood and urine tests	Day -1 (Baseline) and up to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urinary albumin excretion	Urine tests	Day -1 (Baseline) and up to Day 15

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Dennis Andress, MD, Renal Global Project Team, Abbott Laboratories

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: November 1, 2011
• First Submitted That Met QC Criteria: November 1, 2011
• First Posted (Estimate): November 3, 2011

Study Record Updates

• Last Update Posted (Estimate): August 22, 2012
• Last Update Submitted That Met QC Criteria: August 21, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Safety; Type 2 diabetes; Kidney disease
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Renal Insufficiency; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: M13-107