Trial Outcomes & Findings for The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion (NCT NCT02406443)

NCT ID: NCT02406443

Last Updated: 2018-04-05

Results Overview

FENA at 3Hrs post-study drug administration after 1 month compared to FENA at 3Hrs post-study drug administration after 1 dose expressed as percent change, sitagliptin vs. placebo

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 36 participants
• Primary outcome timeframe: 3 Hrs post-administration after 1 month and after 1 dose
• Results posted on: 2018-04-05

Participant Flow

Participant milestones

Measure	Experimental Arm sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Overall Study STARTED	18	18
Overall Study COMPLETED	16	16
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion

Baseline characteristics by cohort

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days	Total n=32 Participants Total of all reporting groups
Age, Continuous	60.4 years STANDARD_DEVIATION 7.6 • n=5 Participants	59.3 years STANDARD_DEVIATION 8.8 • n=7 Participants	59.8 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Diabetes Duration	6.0 years n=5 Participants	8.5 years n=7 Participants	8.0 years n=5 Participants
HbA1c (%)	7.18 Percentage STANDARD_DEVIATION 0.97 • n=5 Participants	7.31 Percentage STANDARD_DEVIATION 0.84 • n=7 Participants	7.2 Percentage STANDARD_DEVIATION 0.8 • n=5 Participants

PRIMARY outcome

Timeframe: 3 Hrs post-administration after 1 month and after 1 dose

FENA at 3Hrs post-study drug administration after 1 month compared to FENA at 3Hrs post-study drug administration after 1 dose expressed as percent change, sitagliptin vs. placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Percent Change in Fractional Excretion of Sodium (FENA)	41 percentage of change Standard Deviation 43	-5.0 percentage of change Standard Deviation 31

SECONDARY outcome

Timeframe: 3 Hrs post-administration after 1 month and after 1 dose

Measured GFR (Inulin Clearance) at 3Hrs post study-drug after 1 month compared to Measured GFR at 3Hrs post-study drug after 1 dose, sitagliptin vs. placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change in Glomerular Filtration Rate (GFR)	3.9 ml per min per 1.73 m2 Standard Deviation 20.4	-1.8 ml per min per 1.73 m2 Standard Deviation 17.8

SECONDARY outcome

Timeframe: 3 Hrs post-administration after 1 month and after 1 dose

FELi at 3 Hr post-study drug administration after 1 month compared to FELI at 3hrs post-study drug administration after 1 dose, sitagliptin vs. placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change in Fractional Excretion of Lithium (FELi)	29 percentage of change Standard Deviation 55	7 percentage of change Standard Deviation 44

SECONDARY outcome

Timeframe: 3 Hr vs. baseline after 1 dose

Plasma concentration of SDF-1alpha^1-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change From Baseline in SDF-1alpha^1-67 (Intact) Measured by Immunoaffinity and Tandem Mass Spectrometry	0.5 ng per mL Standard Deviation 0.2	0 ng per mL Standard Deviation 0

SECONDARY outcome

Timeframe: 3Hrs vs baseline after 1 dose

Plasma concentration of SDF-1alpha^3-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change From Baseline in SDF-1alpha^3-67 (Truncated) Measured by Tandem Mass Spectrometry With Antibody-based Affinity Enrichment	-2.0 ng per mL Standard Deviation 0.4	0.4 ng per mL Standard Deviation 0.3

SECONDARY outcome

Timeframe: 3 Hrs post-administration after 1 month and after 1 dose

SBP by Non-Invasive cardiac output monitoring at 3Hrs post- study drug administration after 1 month compared to SBP by Non-invasive cardiac output monitoring at 3Hrs after 1 dose, sitagliptin vs placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring	5.7 mmHg Standard Deviation 9.9	0.0 mmHg Standard Deviation 14.0

SECONDARY outcome

Timeframe: 3 Hrs post-administration after 1 month and after 1 dose

ERPF (para-aminohippurate clearance) 3Hrs post-study drug administration after 1 month compared to ERPF at 3Hhrs post-study drug administration after 1 dose, sitagliptin vs placebo

Outcome measures

Measure	Experimental Arm n=16 Participants sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=16 Participants placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Change in Effective Renal Plasma Flow (ERPF)	31.1 ml per min per 1.73 m2 Standard Deviation 152.1	-24.7 ml per min per 1.73 m2 Standard Deviation 142.8

Adverse Events

Experimental Arm

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Experimental Arm n=17 participants at risk sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Sitaglitpin: Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days	Placebo Arm n=18 participants at risk placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Placebo: Oral tablet (no medicinal ingredients) administered once daily for 28 days
Cardiac disorders Dyspnea	0.00% 0/17 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.	5.6% 1/18 • Number of events 1 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.
Cardiac disorders Presyncope	0.00% 0/17 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.	5.6% 1/18 • Number of events 1 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.
Gastrointestinal disorders Lower GI Bleed	5.9% 1/17 • Number of events 1 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.	0.00% 0/18 The intention to treat population at risk was 17 for the experimental arm and 18 for the placebo arm, and the final per-protocol population was 16 per arm. 1 participant in the experimental arm was withdrawn due to lower GI bleeding after randomization, and 2 participants in the placebo arm were withdrawn, 1 due to dyspnea and 1 due to presyncope after randomization.

Other adverse events

Adverse event data not reported

Additional Information

University Health Network

Renal Physiology Laboratory

Phone: 416-340-4800

Email: vesta.lai@uhn.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place