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The study was prematurely terminated due to enrollment challenges.
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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),
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IW-1701 | Experimental | Single 5-mg dose of IW-1701 administered orally |
|
| Placebo | Placebo Comparator | Matching placebo administered orally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olinciguat | Drug | oral tablet |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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). | 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). | 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). |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other inclusion and exclusion criteria specified in the protocol.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Connecticut Clinical Research Foundation, Gastroenterology Institute | Bristol | Connecticut | 06010 | United States | ||
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Matching placebo administered orally |
| FG001 | Olinciguat | Single 5-mg dose of olinciguat administered orally |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo or Olinciguat | Matching placebo administered orally or single 5-mg dose of olinciguat administered orally |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All participants who received study drug were included in the Safety Population and were evaluated for according to the treatment they actually received. | Posted | Count of Participants | 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. |
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Matching placebo administered orally | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Presyncope | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
The study was prematurely terminated due to enrollment challenges after 9 participants had completed the study. The small number of participants limits the interpretation of study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Medical Director | Cyclerion Therapeutics, Inc. | 1-857-327-8778 | info@cyclerion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 3, 2017 | Apr 8, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 23, 2018 | Apr 8, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D004931 | Esophageal Achalasia |
| ID | Term |
|---|---|
| D015154 | Esophageal Motility Disorders |
| D003680 | Deglutition Disorders |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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| Matching Placebo |
| Drug |
oral tablet |
|
| 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). | 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) | 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). | 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). | 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) | 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) | 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) | 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). |
| Mayo Clinic |
| Rochester |
| Minnesota |
| 55905 |
| United States |
| Washington University in St. Louis - School of Medicine | St Louis | Missouri | 63110 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition | Salt Lake City | Utah | 84132 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
| Primary | 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). | Pharmacodynamic (PD) Population: All participants who received study drug had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | seconds | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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). | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | seconds | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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). | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | mm Hg | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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). | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | mm Hg | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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) | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | cm | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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). | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | cm | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | 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). | PD Population: All participants who received study drug and had at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | cm | Day 1: predose (baseline) and 3 hours (+15 minutes) postdose |
|
|
|
| Primary | Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast) | Pharmacokinetic (PK) Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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). |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) | PK Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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). |
|
|
|
| Primary | Time of Maximum Observed Plasma Concentration (Tmax) | PK Population: All participants who received olinciguat and had at least 1 evaluable postdose PK parameter assessment | Posted | Median | Full Range | hours | 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). |
|
|
|
| 2 |
| 0 |
| 2 |
| 1 |
| 2 |
| EG001 | Olinciguat | Single 5-mg dose of olinciguat administered orally | 0 | 7 | 0 | 7 | 2 | 7 |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
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.
| D004066 | Digestive System Diseases |