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

NCT02931565 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: C1701-201
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

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

Conditions

Achalasia

Outcome Measures

Primary Outcomes (11)

• 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).

  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).

Study Arms (2)

IW-1701

EXPERIMENTAL

Single 5-mg dose of IW-1701 administered orally

Drug: Olinciguat

Placebo

PLACEBO COMPARATOR

Matching placebo administered orally

Drug: Matching Placebo

Interventions

Olinciguat DRUG

oral tablet

Also known as: IW-1701

IW-1701

Matching Placebo DRUG

oral tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cyclerion Therapeutics: lead

Study Sites (5)

Connecticut Clinical Research Foundation, Gastroenterology Institute

Bristol, Connecticut, 06010, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis - School of Medicine

St Louis, Missouri, 63110, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Esophageal Achalasia

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Senior Medical Director
• Organization: Cyclerion Therapeutics, Inc.

info@cyclerion.com

1-857-327-8778

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2016
• First Posted: October 13, 2016
• Study Start: April 6, 2017
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: May 4, 2021
• Results First Posted: May 4, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

US (5)