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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- Change From Baseline in 5 Minute IBH
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
IW-1701
Single 5-mg dose of IW-1701 administered orally
干预措施: Olinciguat (Drug)
Placebo
Matching placebo administered orally
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Change From Baseline in 5 Minute IBH
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
次要结局
未报告次要终点