Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
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. |
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. |
|
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). |
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). |
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). |
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). |
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) |
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). |
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). |
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) |
|
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) |
|
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) |
|
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). |
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