Clinical trial NCT02931565: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Achalasia
Lead sponsor: Cyclerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-10-13
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
timeFrame: 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.
measure: Change From Baseline in Supine Bolus Flow Time (BFT)
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in Upright BFT
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in Supine Integrated Relaxation Pressure (IRP)
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in Upright IRP
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in 1 Minute Impedance Bolus Height (IBH)
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in 2 Minute IBH
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Change From Baseline in 5 Minute IBH
timeFrame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
measure: Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast)
timeFrame: 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).
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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).
measure: Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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).
Secondary outcomes:
Other outcomes:
Locations:
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation, Gastroenterology Institute
state: Connecticut
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis - School of Medicine
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition
state: Utah
Study officials:
References: