A Phase 2 interventional study of Olinciguat and Matching Placebo in Achalasia, sponsored by Cyclerion Therapeutics. Terminated at 5 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-05-04.
Sponsored by Cyclerion Therapeutics · Phase 2, Interventional, and Treatment
The objectives of this study are as follows:
In participants with primary Type I or II achalasia, following a single 5-mg dose of olinciguat (IW-1701),
Key Inclusion Criteria:
Key Exclusion Criteria:
Other inclusion and exclusion criteria specified in the protocol.
Single 5-mg dose of IW-1701 administered orally
Drug: Olinciguat
Matching placebo administered orally
Drug: Matching Placebo
oral tablet
Also known as: IW-1701
oral tablet
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
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.
Time frame: 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.
Change From Baseline in Supine Bolus Flow Time (BFT)
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in Upright BFT
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in Supine Integrated Relaxation Pressure (IRP)
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in Upright IRP
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in 1 Minute Impedance Bolus Height (IBH)
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)
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in 2 Minute IBH
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Change From Baseline in 5 Minute IBH
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).
Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast)
Time frame: 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).
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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).
Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: 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).
| Milestone | Placebo | Olinciguat |
|---|---|---|
| Started | 2 | 7 |
| Completed | 2 | 7 |
| Not completed | 0 | 0 |
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.
| Participants | Placebo | Olinciguat |
|---|---|---|
| >= 1 TEAE | 1 | 2 |
| Deaths | 0 | 0 |
| >= 1 SAE | 0 | 0 |
| >= 1 ADO | 0 | 0 |
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).
| seconds | Placebo | Olinciguat |
|---|---|---|
| Baseline | 1.240 ± NA | 0.297 ± 0.727 |
| Change From Baseline | -0.570 ± NA | 0.270 ± 0.657 |
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).
| seconds | Placebo | Olinciguat |
|---|---|---|
| Baseline | 1.160 ± NA | 0.002 ± 0.004 |
| Change From Baseline | 0.580 ± NA | 0.143 ± 0.356 |
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).
| mm Hg | Placebo | Olinciguat |
|---|---|---|
| Baseline | 17.950 ± 9.263 | 45.214 ± 15.730 |
| Change From Baseline | 3.900 ± 8.556 | -7.471 ± 7.456 |
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).
| mm Hg | Placebo | Olinciguat |
|---|---|---|
| Baseline | 17.650 ± 7.142 | 45.757 ± 12.164 |
| Change From Baseline | 3.850 ± 9.122 | -9.350 ± 5.613 |
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)
| cm | Placebo | Olinciguat |
|---|---|---|
| Baseline | 4.60 ± NA | 15.80 ± 3.81 |
| Change From Baseline | 10.90 ± NA | -2.76 ± 4.66 |
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).
| cm | Placebo | Olinciguat |
|---|---|---|
| Baseline | 2.90 ± NA | 14.73 ± 4.32 |
| Change From Baseline | 8.90 ± NA | -2.37 ± 3.88 |
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).
| cm | Placebo | Olinciguat |
|---|---|---|
| Baseline | 2.30 ± NA | 13.07 ± 3.62 |
| Change from Baseline | 5.80 ± NA | -1.52 ± 4.99 |
| h*ng/mL | Olinciguat |
|---|---|
| Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast) | 700.8 ± 17.4 |
| ng/mL | Olinciguat |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 43.4 ± 17.7 |
| hours | Olinciguat |
|---|---|
| Time of Maximum Observed Plasma Concentration (Tmax) | 5.0 (4 to 8) |
Collected over 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).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Olinciguat | 0/7 (0%) | 0/7 (0%) | 2/7 (28.6%) |
| Event | Placebo | Olinciguat |
|---|---|---|
| DizzinessNervous system disorders | 1/2 | 0/7 |
| PresyncopeNervous system disorders | 0/2 | 1/7 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 0/2 | 1/7 |
Due to privacy and reidentification concerns (rare disease, small population), the arms are combined for Baseline characteristics, and race and ethnicity data are not provided.
| Age, Continuous(years) | Placebo or Olinciguat |
|---|---|
| Mean | 46.6 ± 14.4 |
| Sex: Female, Male(Participants) | Placebo or Olinciguat |
|---|---|
| Female | 3 |
| Male | 6 |
| Ethnicity (NIH/OMB)(Participants) | Placebo or Olinciguat |
|---|---|
| Hispanic or Latino | NA |
| Not Hispanic or Latino | NA |
| Unknown or Not Reported | NA |
| Race (NIH/OMB)(Participants) | Placebo or Olinciguat |
|---|---|
| American Indian or Alaska Native | NA |
| Asian | NA |
| Native Hawaiian or Other Pacific Islander | NA |
| Black or African American | NA |
| White | NA |
| More than one race | NA |
| Unknown or Not Reported | NA |
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Cyclerion Therapeutics