Study of IW-1701, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Type I or II Achalasia

Phase 2

Terminated

• Conditions: Achalasia
• Interventions: Drug: Matching Placebo; Drug: Olinciguat

• Registration Number: NCT02931565
• Lead Sponsor: Cyclerion Therapeutics

Brief Summary

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),

* To assess the safety and tolerability

* To determine the effects on measures of esophageal function by high-resolution impedance manometry (HRIM)

* To determine the pharmacokinetic (PK) parameters

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-11
• Study First Submitted QC: 2016-10-12
• Study First Posted: 2016-10-13
• Study Start: 2017-04-06
• Primary Completion: 2018-05-01
• Study Completion: 2018-05-01
• Disposition First Submitted: 2019-06-04
• Disposition First Submitted QC: 2019-06-04
• Disposition First Posted: 2019-06-06
• Status Verified: 2021-04
• Results First Submitted: 2021-04-08
• Results First Submitted QC: 2021-04-08
• Last Update Submitted: 2021-04-08
• Results First Posted: 2021-05-04
• Last Update Posted: 2021-05-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• Patient has a diagnosis of primary Type I or II achalasia.
• Patient has no contraindications to the performance of the baseline and postdose HRIM procedures per Investigator discretion.

Key

Exclusion Criteria

• Patient has had any prior esophageal, periesophageal, or gastric surgery, or treatment with sclerosing agent.
• More than 1 pneumatic dilation procedure to a diameter of > 2 cm in their lifetime.
• Pneumatic dilation procedure to a diameter of > 2 cm within 1 year prior to randomization. Prior bougie dilation(s) or pneumatic dilation(s) ≤ 2 cm are allowed.
• Prior esophageal injection of botulinum toxin (Botox) within 6 months prior to randomization or more than 2 esophageal Botox injection procedures in their lifetime.
• Patients with malignant or premalignant esophageal lesions.
• Patient has taken any drug that can affect gastrointestinal (GI) motility in the 72 hours before check-in through discharge from the clinic.

Other inclusion and exclusion criteria specified in the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Matching Placebo	Matching placebo administered orally
IW-1701	Olinciguat	Single 5-mg dose of IW-1701 administered orally

Primary Outcome Measures

Name	Time	Method
Change From Baseline in 5 Minute IBH	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)	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.	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 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).
Change From Baseline in Upright IRP	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).
Change From Baseline in Upright BFT	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).
Change From Baseline in Supine Integrated Relaxation Pressure (IRP)	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).
Change From Baseline in 1 Minute Impedance Bolus Height (IBH)	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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)
Change From Baseline in 2 Minute IBH	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).
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).
Change From Baseline in Supine Bolus Flow Time (BFT)	Day 1: predose (baseline) and 3 hours (+15 minutes) postdose	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).

Trial Locations

Locations (5)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition; 🇺🇸 Salt Lake City, Utah, United States

Connecticut Clinical Research Foundation, Gastroenterology Institute; 🇺🇸 Bristol, Connecticut, United States

Washington University in St. Louis - School of Medicine; 🇺🇸 Saint Louis, Missouri, United States