A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge
研究概览
简要总结
The purpose of this study is to determine whether oral temanogrel improves digital blood flow in participants with Raynaud's phenomenon secondary to systemic sclerosis (SSc-RP) as a potential safe and effective treatment for symptoms associated with SSc-RP.
详细描述
The study will be conducted in 2 stages: Stage A and Stage B. In both stages, participants will be equally randomized in a double-blind manner to a 3-period crossover treatment sequence. Separate cohorts of participants will participate in each stage. In Stage A, participants will be treated with two dose levels of temanogrel and placebo. Doses in Stage B will be determined based on the results of Stage A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Raynaud's phenomenon (defined as a history of digital cold sensitivity associated with color changes of cyanosis and pallor, with on average at least 5 attacks per week during the winter period) secondary to systemic sclerosis (SSc)
- •Both men and women participants agree to use a highly effective method of birth control if the possibility of conception exists
- •Body mass index 18.0 to 40.0 kilograms per square meter (kg/m^2), inclusive
排除标准
- •Active digital ulcer(s), recent history (within 3 months of Screening) of digital ulcers, or history of recurrent digital ulcerations that in the opinion of the Investigator increase the likelihood of developing a digital ulcer during the course of the study. Any history of gangrene, amputations, or other critical digital ischemic event
- •Raynaud's phenomenon due to any cause other than SSc
- •Severe gastrointestinal complications related to SSc that in the opinion of the Investigator could significantly affect study drug absorption
- •History of gastrointestinal bleeding or active gastric or duodenal ulcers
研究组 & 干预措施
Temanogrel (Stage B Dose 1)
干预措施: Temanogrel (Drug)
Temanogrel (Stage A Dose 1)
干预措施: Temanogrel (Drug)
Temanogrel (Stage A Dose 2)
干预措施: Temanogrel (Drug)
Placebo (Stage A)
干预措施: Placebo (Drug)
Temanogrel (Stage B Dose 2)
干预措施: Temanogrel (Drug)
Placebo (Stage B)
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge
时间窗: 30 minutes following a cold challenge
Area under the curve for rewarming of digital blood flow after 30 minutes following a cold challenge was assessed. Area under the curve was defined as the area under the skin temperature curve and rewarming was a delicate phase of therapeutic hypothermia (TH). A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Rewarming was assessed by infrared (IR) thermography which was an indirect method for evaluation of blood flow based on imaging skin temperature. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).
Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge
时间窗: 30 minutes following a cold challenge
Area under the curve for reperfusion of digital blood flow after 30 minutes following a cold challenge was assessed. A cold challenge was conducted by immersing hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Reperfusion was assessed with laser speckle contrast imaging (LSCI) which was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu (and also pu\*seconds) are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).
次要结局
- Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)(30 minutes following a cold challenge)
- Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography(Initial 2 minutes following a cold challenge)
- Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography(30 minutes following a cold challenge)
- Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography(30 minutes following a cold challenge)
- Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI(30 minutes following a cold challenge)
- AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography(Initial 2 minutes following a cold challenge)
- Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI(Initial 2 minutes following a cold challenge)
- Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI(Initial 2 minutes following a cold challenge)
- Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI(30 minutes following a cold challenge)
- Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI(30 minutes following a cold challenge)
- Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography(5 minutes pre-dose, 5 minutes post-dose)
- Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI(5 minutes pre-dose, 5 minutes post-dose)
- Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography(5 minutes pre-dose, 5 minutes post-dose)
- Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI(5 minutes pre-dose, 5 minutes post-dose)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days))