Trial Outcomes & Findings for Study of IW-1701, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Type I or II Achalasia (NCT NCT02931565)
NCT ID: NCT02931565
Last Updated: 2021-05-04
Results Overview
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is any AE occurring at any dose that results in any of the following outcomes: death; life-threatening: the patient was at immediate risk of death from the reaction as it occurred; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical event. Deaths and SAEs include those that occurred on or after the participant signed the informed consent at the Screening Visit through the End-of-Trial Visit. TEAEs are defined as adverse events that occurred on/after administration of the double-blind study drug and within 72 hours after the double-blind study drug administration.
TERMINATED
PHASE2
9 participants
Deaths, SAEs, and AEs: from enrollment through end-of-trial visit Day 21 (±7 days). TEAEs: from first dose of study drug through 72 hours postdose.
2021-05-04
Participant Flow
Up to 20 participants were planned to be randomized in a 3:1 ratio to receive either olinciguat or matching placebo. The study was prematurely terminated due to enrollment challenges after 9 participants had completed the study.
Participant milestones
| Measure |
Placebo
Matching placebo administered orally
|
Olinciguat
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
7
|
|
Overall Study
COMPLETED
|
2
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of IW-1701, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Type I or II Achalasia
Baseline characteristics by cohort
| Measure |
Placebo or Olinciguat
n=9 Participants
Matching placebo administered orally or single 5-mg dose of olinciguat administered orally
|
|---|---|
|
Age, Continuous
|
46.6 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
NA Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
NA Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
NA Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Deaths, SAEs, and AEs: from enrollment through end-of-trial visit Day 21 (±7 days). TEAEs: from first dose of study drug through 72 hours postdose.Population: All participants who received study drug were included in the Safety Population and were evaluated for according to the treatment they actually received.
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is any AE occurring at any dose that results in any of the following outcomes: death; life-threatening: the patient was at immediate risk of death from the reaction as it occurred; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical event. Deaths and SAEs include those that occurred on or after the participant signed the informed consent at the Screening Visit through the End-of-Trial Visit. TEAEs are defined as adverse events that occurred on/after administration of the double-blind study drug and within 72 hours after the double-blind study drug administration.
Outcome measures
| Measure |
Placebo
n=2 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
>= 1 TEAE
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
Deaths
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
>= 1 SAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
>= 1 ADO
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: Pharmacodynamic (PD) Population: All participants who received study drug had at least 1 postdose PD assessment.
Supine BFT defined as the median measurement from the 10 available swallows in supine position as measured by high resolution impedance manometry (HRIM), and determined by the central read (seconds; longer times=more severe achalasia). Change=(postdose supine BFT - predose supine BFT).
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo administered orally
|
Olinciguat
n=6 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in Supine Bolus Flow Time (BFT)
Baseline
|
1.240 seconds
Standard Deviation NA
1 participant in arm
|
0.297 seconds
Standard Deviation 0.727
|
|
Change From Baseline in Supine Bolus Flow Time (BFT)
Change From Baseline
|
-0.570 seconds
Standard Deviation NA
1 participant in arm
|
0.270 seconds
Standard Deviation 0.657
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
Upright BFT defined as the median measurement from the 5 available swallows in the upright position as measured by HRIM, and determined by the central read (seconds; longer times=more severe achalasia). Change = (postdose upright BFT - predose upright BFT).
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in Upright BFT
Baseline
|
1.160 seconds
Standard Deviation NA
1 participant in arm
|
0.002 seconds
Standard Deviation 0.004
|
|
Change From Baseline in Upright BFT
Change From Baseline
|
0.580 seconds
Standard Deviation NA
1 participant in arm
|
0.143 seconds
Standard Deviation 0.356
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
Supine IRP defined as the median measurement from the 10 available swallows in supine position as determined by the central read (mmHg; higher pressure=more severe achalasia), measured by HRIM. Change = (postdose supine IRP - predose supine IRP).
Outcome measures
| Measure |
Placebo
n=2 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in Supine Integrated Relaxation Pressure (IRP)
Baseline
|
17.950 mm Hg
Standard Deviation 9.263
|
45.214 mm Hg
Standard Deviation 15.730
|
|
Change From Baseline in Supine Integrated Relaxation Pressure (IRP)
Change From Baseline
|
3.900 mm Hg
Standard Deviation 8.556
|
-7.471 mm Hg
Standard Deviation 7.456
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
Upright IRP is defined as the median measurement from the 5 available swallows in the supine position as determined by the central read (mmHg; higher pressure=more severe achalasia), measured by HRIM. Change = (postdose upright IRP - predose upright IRP).
Outcome measures
| Measure |
Placebo
n=2 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in Upright IRP
Baseline
|
17.650 mm Hg
Standard Deviation 7.142
|
45.757 mm Hg
Standard Deviation 12.164
|
|
Change From Baseline in Upright IRP
Change From Baseline
|
3.850 mm Hg
Standard Deviation 9.122
|
-9.350 mm Hg
Standard Deviation 5.613
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
1 minute IBH defined by the height in esophagus of 200 mL saline bolus 1 minute post-bolus as measured by HRIM and determined by the central read (cm; greater height=more severe achalasia). Change = (postdose height 1 min IBH - predose height 1 min IBH)
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in 1 Minute Impedance Bolus Height (IBH)
Baseline
|
4.60 cm
Standard Deviation NA
1 participant in arm
|
15.80 cm
Standard Deviation 3.81
|
|
Change From Baseline in 1 Minute Impedance Bolus Height (IBH)
Change From Baseline
|
10.90 cm
Standard Deviation NA
1 participant in arm
|
-2.76 cm
Standard Deviation 4.66
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
2 minute IBH defined by the height in esophagus of 200 mL saline bolus 2 minutes post-bolus as measured by HRIM and determined by the central read (cm; greater height=more severe achalasia). Change = (postdose height 2 min IBH - predose height 2 min IBH).
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo administered orally
|
Olinciguat
n=7 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in 2 Minute IBH
Baseline
|
2.90 cm
Standard Deviation NA
1 participant in arm
|
14.73 cm
Standard Deviation 4.32
|
|
Change From Baseline in 2 Minute IBH
Change From Baseline
|
8.90 cm
Standard Deviation NA
1 participant in arm
|
-2.37 cm
Standard Deviation 3.88
|
PRIMARY outcome
Timeframe: Day 1: predose (baseline) and 3 hours (+15 minutes) postdosePopulation: PD Population: All participants who received study drug and had at least 1 postdose PD assessment.
5 minute IBH defined by the height in esophagus of 200 mL saline bolus 5 minutes post-bolus as determined by the central read (cm; greater height=more severe achalasia). Change = (postdose height 5 min IBH - predose height 5 min IBH).
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo administered orally
|
Olinciguat
n=6 Participants
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Change From Baseline in 5 Minute IBH
Baseline
|
2.30 cm
Standard Deviation NA
1 participant in arm
|
13.07 cm
Standard Deviation 3.62
|
|
Change From Baseline in 5 Minute IBH
Change from Baseline
|
5.80 cm
Standard Deviation NA
1 participant in arm
|
-1.52 cm
Standard Deviation 4.99
|
PRIMARY outcome
Timeframe: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).Population: Pharmacokinetic (PK) Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment.
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo administered orally
|
Olinciguat
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast)
|
700.8 h*ng/mL
Geometric Coefficient of Variation 17.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).Population: PK Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment.
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo administered orally
|
Olinciguat
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
43.4 ng/mL
Geometric Coefficient of Variation 17.7
|
—
|
PRIMARY outcome
Timeframe: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).Population: PK Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo administered orally
|
Olinciguat
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax)
|
5.0 hours
Interval 4.0 to 8.0
|
—
|
Adverse Events
Placebo
Olinciguat
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=2 participants at risk
Matching placebo administered orally
|
Olinciguat
n=7 participants at risk
Single 5-mg dose of olinciguat administered orally
|
|---|---|---|
|
Nervous system disorders
Presyncope
|
0.00%
0/2 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
14.3%
1/7 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
|
Nervous system disorders
Dizziness
|
50.0%
1/2 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
0.00%
0/7 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/2 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
14.3%
1/7 • Deaths and SAEs: from enrollment through end-of trial visit Day 21 (±7 days). AEs: from first dose of study drug through Day 2 (±72 hours).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI may publish or disclose the results of the study 24 months after final data lock provided that sponsor can review the publication prior to public release, sponsor can request removal of confidential information of sponsor (not including results of trial), and sponsor can request a publication delay in order to protect potentially patentable information. Furthermore, if a publication committee is developing an initial publication, PI is to delay disclosure until that publication is published.
- Publication restrictions are in place
Restriction type: OTHER