Trial Outcomes & Findings for A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria (NCT NCT03217591)

Last Updated: 2022-09-15

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. Causality relationship to study drug was per Investigator assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

156 participants

Primary outcome timeframe

Day 1 up to Day 115

Results posted on

2022-09-15

Participant Flow

This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the safety and efficacy of praliciguat (IW-1973) in participants with type 2 diabetes mellitus with albuminuria who were on a stable regimen of renin-angiotensin system inhibitors.

A total of 156 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Placebo Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.
Overall Study STARTED	54	50	52
Overall Study COMPLETED	51	47	42
Overall Study NOT COMPLETED	3	3	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.
Overall Study Adverse Event	1	2	6
Overall Study Withdrawal by Subject	0	1	3
Overall Study Lost to Follow-up	1	0	0
Overall Study Protocol Violation	1	0	1

Baseline Characteristics

A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg n=50 Participants Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg n=52 Participants Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Total n=156 Participants Total of all reporting groups
Age, Customized 18 - 45	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Age, Customized >45 - 65	26 Participants n=5 Participants	25 Participants n=7 Participants	23 Participants n=5 Participants	74 Participants n=4 Participants
Age, Customized >65	28 Participants n=5 Participants	24 Participants n=7 Participants	27 Participants n=5 Participants	79 Participants n=4 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants	53 Participants n=4 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	34 Participants n=7 Participants	32 Participants n=5 Participants	103 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	30 Participants n=7 Participants	30 Participants n=5 Participants	85 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	20 Participants n=7 Participants	22 Participants n=5 Participants	71 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	37 Participants n=4 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants	33 Participants n=7 Participants	37 Participants n=5 Participants	111 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 115

Population: Safety Population consisted of all randomized participants who received at least 1 dose of study drug. Participants in this population were summarized according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg n=50 Participants Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg n=52 Participants Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat Overall Participants were randomized to receive both 20 mg and 40 mg praliciguat orally for 12 weeks.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs Any TEAE	24 Participants	21 Participants	22 Participants	—
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs Study drug-related TEAEs	6 Participants	3 Participants	10 Participants	—

PRIMARY outcome

Timeframe: Baseline; Week 8 to Week 12

Population: Intent-to-Treat Population consisted of all randomized participants who received at least 1 dose of study drug. Participants in this population were evaluated according to the treatment group they were assigned to at Randomization.

Urine samples were collected for the analysis of UACR. UACR (milligrams per gram \[mg/g\]) was calculated as urine albumin (mg per deciliter \[mg/dL\]) / urine creatinine (g/dL). Change from Baseline was calculated as the average of the UCAR values at Weeks 8 and 12 minus the Baseline value. Data were analyzed using a mixed-effects model repeated measures (MMRM) analysis with change from Baseline in log-transformed UACR as the response variable, treatment, visit, treatment-by visit interaction, and Baseline estimated glomerular filtration rate stratum as fixed effects, Baseline log-transformed UACR and Baseline mean arterial pressure as covariates, and unstructured as the variance-covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg n=50 Participants Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg n=52 Participants Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat Overall n=102 Participants Participants were randomized to receive both 20 mg and 40 mg praliciguat orally for 12 weeks.
Percent Change From Baseline in Urine Albumin Creatinine Ratio (UACR) Over Weeks 8 and 12	-14.8 Percent Change Interval -27.7 to 0.4	-28.4 Percent Change Interval -39.4 to -15.3	-27.3 Percent Change Interval -39.2 to -13.1	-27.8 Percent Change Interval -36.3 to -18.3

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Praliciguat 20 mg

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Praliciguat 40 mg

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=54 participants at risk Participants were randomized to receive matching placebo orally for 12 weeks: 1 week of twice daily (BID) dosing (Days 1 through 7) followed by 11 weeks of once daily (QD) dosing.	Praliciguat 20 mg n=50 participants at risk Participants were randomized to receive praliciguat 20 milligrams (mg) orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.	Praliciguat 40 mg n=52 participants at risk Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 1 week of BID dosing (Days 1 through 7) followed by 11 weeks of QD dosing.
Respiratory, thoracic and mediastinal disorders Bronchitis	1.9% 1/54 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/52 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.9% 1/54 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/52 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.9% 1/54 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/52 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
General disorders Chest pain	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	1.9% 1/52 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Syncope	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	3.8% 2/52 • Number of events 2 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	2.0% 1/50 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/52 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	1.9% 1/52 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	1.9% 1/52 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/54 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	0.00% 0/50 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.	1.9% 1/52 • Number of events 1 • From first dose of study drug (Day 1) up to Follow-up Visit (Day 115) TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.

Other adverse events

Additional Information

Akebia Therapeutics

Phone: 6178446128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place