Trial Outcomes & Findings for Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease (NCT NCT01752985)

NCT ID: NCT01752985

Last Updated: 2019-07-30

Results Overview

The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

319 participants

Primary outcome timeframe

Baseline, Weeks 2, 4, 8, 12, and 16 (Follow-up)

Results posted on

2019-07-30

Participant Flow

319 were enrolled, 110 completed screening, rest 209 discontinued: (Main reason:did not meet study criteria). Of 110 screened, 98 entered Placebo Lead-in period of which 89 completed period, rest 9 discontinued (2 due to Admin. reason, 3 no longer met study criteria, 2 AEs and 2 were lost to follow-up.)1 was randomized but declined treatment

Participant milestones

Participant milestones
Measure
BMS-813160 150 mg QD
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Treatment Period
STARTED
29
30
29
Treatment Period
COMPLETED
25
27
24
Treatment Period
NOT COMPLETED
4
3
5
Follow-up Period
STARTED
28
27
26
Follow-up Period
COMPLETED
28
27
26
Follow-up Period
NOT COMPLETED
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
BMS-813160 150 mg QD
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Treatment Period
Subject request to discontinue treatment
1
0
1
Treatment Period
Subject no longer meets study criteria
0
1
1
Treatment Period
Adverse Event
2
1
2
Treatment Period
Withdrawal by Subject
1
1
0
Treatment Period
Lost to Follow-up
0
0
1

Baseline Characteristics

Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
BMS-813160 150 mg QD
n=29 Participants
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 Participants
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
n=29 Participants
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Total
n=88 Participants
Total of all reporting groups
Age, Continuous
63.9 Years
STANDARD_DEVIATION 9.58 • n=5 Participants
60.2 Years
STANDARD_DEVIATION 8.31 • n=7 Participants
60.6 Years
STANDARD_DEVIATION 11.52 • n=5 Participants
61.5 Years
STANDARD_DEVIATION 9.90 • n=4 Participants
Age, Customized
<65 years
14 Participants
n=5 Participants
17 Participants
n=7 Participants
17 Participants
n=5 Participants
48 Participants
n=4 Participants
Age, Customized
>=65 years
15 Participants
n=5 Participants
13 Participants
n=7 Participants
12 Participants
n=5 Participants
40 Participants
n=4 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
7 Participants
n=7 Participants
8 Participants
n=5 Participants
17 Participants
n=4 Participants
Sex: Female, Male
Male
27 Participants
n=5 Participants
23 Participants
n=7 Participants
21 Participants
n=5 Participants
71 Participants
n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, and 16 (Follow-up)

Population: The analysis was performed in all the participants who received any study drug. Here, 'n' signifies evaluable participants for specified categories in respective treatment arms.

The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period.

Outcome measures

Outcome measures
Measure
BMS-813160 150 mg QD
n=29 Participants
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 Participants
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
n=29 Participants
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Week 2
5.78 Percent Change
Standard Deviation 48.994
3.79 Percent Change
Standard Deviation 62.795
2.05 Percent Change
Standard Deviation 30.771
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Week 4
18.43 Percent Change
Standard Deviation 62.661
5.81 Percent Change
Standard Deviation 83.274
1.46 Percent Change
Standard Deviation 40.051
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Week 8
19.49 Percent Change
Standard Deviation 65.381
9.87 Percent Change
Standard Deviation 56.557
5.68 Percent Change
Standard Deviation 43.659
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Week 12
6.91 Percent Change
Standard Deviation 56.666
29.16 Percent Change
Standard Deviation 78.69
8.91 Percent Change
Standard Deviation 54.025
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Week 16
0.97 Percent Change
Standard Deviation 61.72
20.63 Percent Change
Standard Deviation 85.578
23.77 Percent Change
Standard Deviation 70.411

SECONDARY outcome

Timeframe: From the date of subject's written consent until 30 days post discontinuation of dosing, assessed up to 26 months

Population: The analysis was performed in all the participants who received any study drug.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.

Outcome measures

Outcome measures
Measure
BMS-813160 150 mg QD
n=29 Participants
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 Participants
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
n=29 Participants
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events
SAEs
3 Participants
3 Participants
1 Participants
Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events
Death
0 Participants
1 Participants
0 Participants
Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events
Other (Non-Serious) Adverse Events 5 % cut-off
3 Participants
2 Participants
4 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: The analysis was performed in all the participants who received any study drug.

12-lead ECGs were performed before and 1 hour after dosing at Weeks 0, 2 and 4. ECGs were recorded after the participant has been supine for at least 5 minutes. The PR interval was defined as the beginning of the P wave to the beginning of the QRS complex, and represents the time taken by electrical impulse to travel from the sinus node through the atrioventricular (AV) node. The QRS complex represented the rapid depolarization of the right and left ventricles. The QT interval was defined as the time from the start of the Q wave to the end of the T wave, and represents the time taken for ventricular depolarization and repolarization. Participants were evaluated for abnormal ECG intervals. Criteria's for abnormality were PR \>200, QRS \>120, QT \>500, QTcF \>450, Change From Baseline \>30 milliseconds (msec).

Outcome measures

Outcome measures
Measure
BMS-813160 150 mg QD
n=29 Participants
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 Participants
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
Placebo
n=29 Participants
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks and were followed up for 4 weeks post treatment.
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
PR >200 msec
8 Participants
8 Participants
4 Participants
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
QRS >120 msec
3 Participants
3 Participants
3 Participants
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
QT >500 msec
0 Participants
1 Participants
0 Participants
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
QTcF >450 msec
7 Participants
5 Participants
6 Participants
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
Change from baseline in QT >30 msec
8 Participants
6 Participants
4 Participants
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
Change from baseline in QTcF >30 msec
4 Participants
3 Participants
1 Participants

SECONDARY outcome

Timeframe: Pre-dose at Week 2, 4, 8, 12 and 0.5, 1, 2, 4, and 6 hours post-dose at Week 12

Population: The analysis was planned to be performed in the Pharmacokinetic (PK) analysis set which included all participants who receive a dose of study drug and have adequate PK concentration-time data. Data was not collected for any participants due to termination of the study

Ctrough is the minimum estimated plasma concentration at steady state.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12

Population: The analysis was planned to be performed in the Pharmacokinetic (PK) analysis set which included all participants who receive a dose of study drug and have adequate PK concentration-time data. Data was not collected for any participants due to termination of the study

AUC(0-6 h) is the area under the plasma concentration-time curve from pre-dose (0 h) to 6 h post-dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12

Population: The analysis was planned to be performed in the Pharmacokinetic (PK) analysis set which included all participants who receive a dose of study drug and have adequate PK concentration-time data.Data was not collected for any participants due to termination of the study

CLr was calculated by dividing the total amount excreted in the urine from 0 to 6 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The renal function was classified based on estimated glomerular filtration rate as normal (\>=90 mL/min/1.73 m\^2), mildly impaired (60-89 mL/min/1.73 m\^2), moderately impaired stage 3A (45-59 mL/min/1.73 m\^2), and moderately impaired stage 3B (30-44 L/min/1.73 m\^2).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8 and 12

Population: Data was not collected for any participants due to termination of the study

The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period. The effect of BMS-813160 on urinary albumin excretion as measured by UACR values in participants with diabetic kidney disease after 12 weeks of treatment was assessed. The model included treatment group as a main effect, and the log of baseline UACR values, as well as baseline values of eGFR, blood pressure, blood glucose and lipid levels, as covariates.

Outcome measures

Outcome data not reported

Adverse Events

BMS-813160 150 mg QD

Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths

BMS-813160 300 mg BID

Serious events: 3 serious events
Other events: 2 other events
Deaths: 1 deaths

Placebo

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
BMS-813160 150 mg QD
n=29 participants at risk
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 participants at risk
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks.
Placebo
n=29 participants at risk
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks.
Vascular disorders
Arterial occlusive disease
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Cardiac disorders
Angina pectoris
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Cardiac disorders
Coronary artery occlusion
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Cardiac disorders
Angina unstable
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Nervous system disorders
Transient ischaemic attack
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
General disorders
Death
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Skin and subcutaneous tissue disorders
Eczema
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Metabolism and nutrition disorders
Hypoglycaemia
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Infections and infestations
Lobar pneumonia
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months

Other adverse events

Other adverse events
Measure
BMS-813160 150 mg QD
n=29 participants at risk
Participants received BMS-813160 150 mg, capsule, orally along with matching placebo in Ante Meridiem (AM) and 2 Placebo matching with BMS-813160, capsules, orally in Post Meridiem (PM) for 12 weeks. Participants were followed up for 4 weeks post treatment.
BMS-813160 300 mg BID
n=30 participants at risk
Participants received 2 BMS-813160 150 mg capsules, orally, twice daily (2\*150 in AM and 2\*150 in PM) for 12 weeks.
Placebo
n=29 participants at risk
Participants received BMS-813160 matching placebo capsules, orally, twice daily in AM and PM for 12 weeks.
General disorders
Oedema peripheral
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
6.7%
2/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
10.3%
3/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
General disorders
Fatigue
10.3%
3/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Gastrointestinal disorders
Diarrhoea
3.4%
1/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
6.9%
2/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Infections and infestations
Urinary Tract Infection
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
6.7%
2/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Musculoskeletal and connective tissue disorders
Back pain
6.9%
2/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Investigations
Blood Creatine Phosphokinase Increased
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
6.7%
2/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Nervous system disorders
Headache
6.9%
2/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
3.3%
1/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Nervous system disorders
Dizziness
6.9%
2/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/30 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
0.00%
0/29 • From the date of participant's written consent until 30 days post discontinuation of dosing, assessed up to 26 months

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Results disclosure agreements

  • Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
  • Publication restrictions are in place

Restriction type: OTHER