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

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Olinciguat

Matching Placebo

About this trial

This is an interventional treatment trial for Achalasia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key 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.

Sites / Locations

Connecticut Clinical Research Foundation, Gastroenterology Institute
Mayo Clinic
Washington University in St. Louis - School of Medicine
Vanderbilt University Medical Center
University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IW-1701

Placebo

Arm Description

Single 5-mg dose of IW-1701 administered orally

Matching placebo administered orally

Outcomes

Primary Outcome Measures

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.

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).

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).

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).

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).

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)

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).

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).

Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast)

Maximum Observed Plasma Concentration (Cmax)

Time of Maximum Observed Plasma Concentration (Tmax)

Secondary Outcome Measures

Full Information

NCT ID

NCT02931565

First Posted

October 11, 2016

Last Updated

April 8, 2021

Sponsor

Cyclerion Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT02931565

Brief Title

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

Official Title

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-dose, Phase 2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IW-1701 in Patients With Achalasia

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Terminated

Why Stopped

The study was prematurely terminated due to enrollment challenges.

Study Start Date

April 6, 2017 (Actual)

Primary Completion Date

May 1, 2018 (Actual)

Study Completion Date

May 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cyclerion Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Achalasia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IW-1701

Arm Type

Experimental

Arm Description

Single 5-mg dose of IW-1701 administered orally

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo administered orally

Intervention Type

Drug

Intervention Name(s)

Olinciguat

Other Intervention Name(s)

IW-1701

Intervention Description

oral tablet

Intervention Type

Drug

Intervention Name(s)

Matching Placebo

Intervention Description

oral tablet

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)

Description

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.

Title

Change From Baseline in Supine Bolus Flow Time (BFT)

Description

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