Raynaud's Phenomenon Secondary to Systemic Sclerosis
Conditions
Keywords
Raynaud's phenomenon, SSc-RP, Systemic sclerosis, SSc, Digital cold sensitivity, Digital blood flow, APD791, Temanogrel
Brief summary
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.
Detailed description
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.
Interventions
DRUGTemanogrel
Participants will receive a single oral dose of temanogrel during the treatment visit.
DRUGPlacebo
Participants will receive a single oral dose of temanogrel matching placebo during the treatment visit.
Sponsors
Arena is a wholly owned subsidiary of Pfizer
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography | 30 minutes following a cold challenge | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Changes in skin temperature at each visit were imaged IR thermography. 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. 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). |
| Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI | 30 minutes following a cold challenge | 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. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. Changes in skin temperature at each visit were imaged using LSCI. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu 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). |
| AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography | Initial 2 minutes following a cold challenge | AUC was defined as the area under the skin temperature curve. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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). |
| Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI | Initial 2 minutes following a cold challenge | 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. LSCI 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. AUC was defined as the area under the skin temperature curve, based on the LSCI results. 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). |
| Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography | Initial 2 minutes following a cold challenge | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. Slope was calculated based on the changes in skin temperature imaged using LSCI and IR thermography during the initial 120 seconds following the cold challenge. 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). |
| Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI | Initial 2 minutes following a cold challenge | A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. LSCI 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. Slope was calculated based on the changes in skin temperature imaged using LSCI during the initial 120 seconds following the cold challenge. 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). |
| Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography | 30 minutes following a cold challenge | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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). |
| Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | 30 minutes following a cold challenge | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 70% recovery was not achieved, the recovery time was set to 30 minutes. 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 From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography | 5 minutes pre-dose, 5 minutes post-dose | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room 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 From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI | 5 minutes pre-dose, 5 minutes post-dose | Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room temperature. LSCI 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 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). |
| Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography | 5 minutes pre-dose, 5 minutes post-dose | The distal dorsal difference was defined as the difference in temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room 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 From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI | 5 minutes pre-dose, 5 minutes post-dose | Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room temperature. LSCI 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 are considered better in the context of this trial. The distal dorsal difference was defined as the difference in perfusion temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. 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). |
| 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) | An adverse event was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. |
| 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 | IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 50% recovery was not achieved, the recovery time was set to 30 minutes. 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). |
| Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI) | 30 minutes following a cold challenge | 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. LSCI 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 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). |
Countries
United Kingdom, United States
Participant flow
Recruitment details
This study was planned to be conducted in 2 stages: Stage A and Stage B. Stage B was not conducted due to early termination of the study.
Pre-assignment details
A total of 13 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Temanogrel 120 mg Then Temanogrel 60 mg Then Placebo Participants received oral temanogrel 120 milligram (mg) (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 1. Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 2 |
| Temanogrel 120 mg Then Placebo Then Temanogrel 60mg Participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 1. Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 2 |
| Temanogrel 60 mg Then Temanogrel 120 mg Then Placebo Participants received temanogrel 60 mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally during treatment period 1 (B). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of period 2. Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 2 |
| Temanogrel 60 mg Then Placebo Then Temanogrel 120 mg Participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally during treatment period 1 (B). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 3. Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 2 |
| Placebo Then Temanogrel 120 mg Then Temanogrel 60 mg Participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of period 2. Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received temanogrel 60 mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 3 |
| Placebo Then Temanogrel 60 mg Then Temanogrel 120 mg Participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 3. Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days. | 2 |
| Total | 13 |
Baseline characteristics
| Characteristic | Temanogrel 120 mg Then Temanogrel 60 mg Then Placebo | Temanogrel 120 mg Then Placebo Then Temanogrel 60mg | Temanogrel 60 mg Then Temanogrel 120 mg Then Placebo | Temanogrel 60 mg Then Placebo Then Temanogrel 120 mg | Placebo Then Temanogrel 120 mg Then Temanogrel 60 mg | Placebo Then Temanogrel 60 mg Then Temanogrel 120 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 4 / 13 | 3 / 13 | 6 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge | 118521 Perfusion units*seconds | Standard Deviation 99257.5 |
| Temanogrel 60 mg | Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge | 120748 Perfusion units*seconds | Standard Deviation 106766.5 |
| Placebo | Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge | 147558 Perfusion units*seconds | Standard Deviation 144265.3 |
Primary
Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge | 43912 Degrees celsius*seconds | Standard Deviation 4399.5 |
| Temanogrel 60 mg | Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge | 44000 Degrees celsius*seconds | Standard Deviation 5308.2 |
| Placebo | Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge | 44530 Degrees celsius*seconds | Standard Deviation 8109.4 |
Secondary
AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography
AUC was defined as the area under the skin temperature curve. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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).
Time frame: Initial 2 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography | 2830 Degree Celsius*seconds | Standard Deviation 193.5 |
| Temanogrel 60 mg | AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography | 2792 Degree Celsius*seconds | Standard Deviation 231.6 |
| Placebo | AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography | 2741 Degree Celsius*seconds | Standard Deviation 327.6 |
Secondary
Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography
The distal dorsal difference was defined as the difference in temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room 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).
Time frame: 5 minutes pre-dose, 5 minutes post-dose
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography | -0.424 Degree Celsius | Standard Deviation 1.7483 |
| Temanogrel 60 mg | Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography | -0.127 Degree Celsius | Standard Deviation 1.7076 |
| Placebo | Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography | 0.332 Degree Celsius | Standard Deviation 1.5891 |
Secondary
Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI
Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room temperature. LSCI 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 are considered better in the context of this trial. The distal dorsal difference was defined as the difference in perfusion temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. 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).
Time frame: 5 minutes pre-dose, 5 minutes post-dose
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI | 3.56 Perfusion units | Standard Deviation 56.143 |
| Temanogrel 60 mg | Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI | 14.16 Perfusion units | Standard Deviation 57.611 |
| Placebo | Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI | 34.86 Perfusion units | Standard Deviation 52.792 |
Secondary
Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI
Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room temperature. LSCI 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 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).
Time frame: 5 minutes pre-dose, 5 minutes post-dose
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI | -0.01 Perfusion units | Standard Deviation 74.996 |
| Temanogrel 60 mg | Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI | -10.13 Perfusion units | Standard Deviation 68.037 |
| Placebo | Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI | -50.16 Perfusion units | Standard Deviation 65.169 |
Secondary
Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room 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).
Time frame: 5 minutes pre-dose, 5 minutes post-dose
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography | 0.576 Degree Celsius | Standard Deviation 3.3539 |
| Temanogrel 60 mg | Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography | -0.278 Degree Celsius | Standard Deviation 2.6927 |
| Placebo | Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography | -0.803 Degree Celsius | Standard Deviation 2.0125 |
Secondary
Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI
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. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. Changes in skin temperature at each visit were imaged using LSCI. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI | 137.9 Perfusion units | Standard Deviation 65 |
| Temanogrel 60 mg | Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI | 141.9 Perfusion units | Standard Deviation 70.47 |
| Placebo | Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI | 159.6 Perfusion units | Standard Deviation 108.87 |
Secondary
Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Changes in skin temperature at each visit were imaged IR thermography. 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. 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography | 25.11 Degree Celsius | Standard Deviation 2.863 |
| Temanogrel 60 mg | Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography | 25.38 Degree Celsius | Standard Deviation 3.541 |
| Placebo | Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography | 25.76 Degree Celsius | Standard Deviation 5.08 |
Secondary
Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)
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. LSCI 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 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI) | 33.67 Perfusion units | Standard Deviation 31.574 |
| Temanogrel 60 mg | Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI) | 30.77 Perfusion units | Standard Deviation 30.898 |
| Placebo | Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI) | 36.04 Perfusion units | Standard Deviation 39.275 |
Secondary
Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography | 23.06 Degree Celsius | Standard Deviation 1.455 |
| Temanogrel 60 mg | Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography | 22.77 Degree Celsius | Standard Deviation 1.77 |
| Placebo | Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography | 22.45 Degree Celsius | Standard Deviation 2.561 |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect.
Time frame: Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
Population: Safety set included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 120 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 4 Participants |
| Temanogrel 120 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Temanogrel 60 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 3 Participants |
| Temanogrel 60 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
Secondary
Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI
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. LSCI 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. AUC was defined as the area under the skin temperature curve, based on the LSCI results. 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).
Time frame: Initial 2 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI | 7353 Perfusion units*seconds | Standard Deviation 4349.9 |
| Temanogrel 60 mg | Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI | 6959 Perfusion units*seconds | Standard Deviation 5093.5 |
| Placebo | Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI | 6384 Perfusion units*seconds | Standard Deviation 5473.9 |
Secondary
Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI
A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. LSCI 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. Slope was calculated based on the changes in skin temperature imaged using LSCI during the initial 120 seconds following the cold challenge. 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).
Time frame: Initial 2 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI | -6.437 Perfusion units/seconds | Standard Deviation 9.5172 |
| Temanogrel 60 mg | Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI | -0.841 Perfusion units/seconds | Standard Deviation 14.1211 |
| Placebo | Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI | 0.652 Perfusion units/seconds | Standard Deviation 11.2937 |
Secondary
Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. Slope was calculated based on the changes in skin temperature imaged using LSCI and IR thermography during the initial 120 seconds following the cold challenge. 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).
Time frame: Initial 2 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 120 mg | Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography | 0.203 Degree Celsius/seconds | Standard Deviation 0.1786 |
| Temanogrel 60 mg | Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography | 0.212 Degree Celsius/seconds | Standard Deviation 0.29 |
| Placebo | Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography | 0.251 Degree Celsius/seconds | Standard Deviation 0.2922 |
Secondary
Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 50% recovery was not achieved, the recovery time was set to 30 minutes. 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 120 mg | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 10.68 Minutes | Standard Deviation 8.59 |
| Temanogrel 120 mg | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 27.06 Minutes | Standard Deviation 6.78 |
| Temanogrel 60 mg | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 9.52 Minutes | Standard Deviation 6.61 |
| Temanogrel 60 mg | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 25.70 Minutes | Standard Deviation 9.12 |
| Placebo | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 23.07 Minutes | Standard Deviation 10.72 |
| Placebo | Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 3.98 Minutes | Standard Deviation 3.63 |
Secondary
Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 70% recovery was not achieved, the recovery time was set to 30 minutes. 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).
Time frame: 30 minutes following a cold challenge
Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 120 mg | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 28.21 Minutes | Standard Deviation 5.01 |
| Temanogrel 120 mg | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 12.99 Minutes | Standard Deviation 9.7 |
| Temanogrel 60 mg | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 26.24 Minutes | Standard Deviation 8.95 |
| Temanogrel 60 mg | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 13.18 Minutes | Standard Deviation 7.27 |
| Placebo | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | IR thermography | 24.53 Minutes | Standard Deviation 10.18 |
| Placebo | Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI | LSCI | 5.34 Minutes | Standard Deviation 4.53 |