Trial Outcomes & Findings for A Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Adult Participants With Raynaud's Phenomenon Secondary to Systemic Sclerosis (NCT NCT04915950)
NCT ID: NCT04915950
Last Updated: 2023-12-22
Results Overview
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).
TERMINATED
PHASE2
13 participants
30 minutes following a cold challenge
2023-12-22
Participant Flow
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.
A total of 13 participants were enrolled and randomized in the study.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Stage A: Treatment Period 1 (1 Day)
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 1 (1 Day)
COMPLETED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Stage A:Washout Period(72hours to 7days)
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A:Washout Period(72hours to 7days)
COMPLETED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A:Washout Period(72hours to 7days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Stage A: Treatment Period 2 (1 Day)
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 2 (1 Day)
COMPLETED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Stage A: Treatment Period 3 (1 Day)
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 3 (1 Day)
COMPLETED
|
2
|
2
|
2
|
2
|
3
|
2
|
|
Stage A: Treatment Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Adult Participants With Raynaud's Phenomenon Secondary to Systemic Sclerosis
Baseline characteristics by cohort
| Measure |
Temanogrel 120 mg Then Temanogrel 60 mg Then Placebo
n=2 Participants
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.
|
Temanogrel 120 mg Then Placebo Then Temanogrel 60mg
n=2 Participants
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.
|
Temanogrel 60 mg Then Temanogrel 120 mg Then Placebo
n=2 Participants
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.
|
Temanogrel 60 mg Then Placebo Then Temanogrel 120 mg
n=2 Participants
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.
|
Placebo Then Temanogrel 120 mg Then Temanogrel 60 mg
n=3 Participants
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.
|
Placebo Then Temanogrel 60 mg Then Temanogrel 120 mg
n=2 Participants
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.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
13 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
44000 Degrees celsius*seconds
Standard Deviation 5308.2
|
44530 Degrees celsius*seconds
Standard Deviation 8109.4
|
PRIMARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
120748 Perfusion units*seconds
Standard Deviation 106766.5
|
147558 Perfusion units*seconds
Standard Deviation 144265.3
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography
|
23.06 Degree Celsius
Standard Deviation 1.455
|
22.77 Degree Celsius
Standard Deviation 1.770
|
22.45 Degree Celsius
Standard Deviation 2.561
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)
|
33.67 Perfusion units
Standard Deviation 31.574
|
30.77 Perfusion units
Standard Deviation 30.898
|
36.04 Perfusion units
Standard Deviation 39.275
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography
|
25.11 Degree Celsius
Standard Deviation 2.863
|
25.38 Degree Celsius
Standard Deviation 3.541
|
25.76 Degree Celsius
Standard Deviation 5.080
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: FAS included all randomized participants, irrespective of whether they received any study treatment.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI
|
137.9 Perfusion units
Standard Deviation 65.00
|
141.9 Perfusion units
Standard Deviation 70.47
|
159.6 Perfusion units
Standard Deviation 108.87
|
SECONDARY outcome
Timeframe: Initial 2 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography
|
2830 Degree Celsius*seconds
Standard Deviation 193.5
|
2792 Degree Celsius*seconds
Standard Deviation 231.6
|
2741 Degree Celsius*seconds
Standard Deviation 327.6
|
SECONDARY outcome
Timeframe: Initial 2 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI
|
7353 Perfusion units*seconds
Standard Deviation 4349.9
|
6959 Perfusion units*seconds
Standard Deviation 5093.5
|
6384 Perfusion units*seconds
Standard Deviation 5473.9
|
SECONDARY outcome
Timeframe: Initial 2 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
0.212 Degree Celsius/seconds
Standard Deviation 0.2900
|
0.251 Degree Celsius/seconds
Standard Deviation 0.2922
|
SECONDARY outcome
Timeframe: Initial 2 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
-0.841 Perfusion units/seconds
Standard Deviation 14.1211
|
0.652 Perfusion units/seconds
Standard Deviation 11.2937
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
25.70 Minutes
Standard Deviation 9.12
|
23.07 Minutes
Standard Deviation 10.72
|
|
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
|
9.52 Minutes
Standard Deviation 6.61
|
3.98 Minutes
Standard Deviation 3.63
|
SECONDARY outcome
Timeframe: 30 minutes following a cold challengePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
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
|
26.24 Minutes
Standard Deviation 8.95
|
24.53 Minutes
Standard Deviation 10.18
|
|
Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI
LSCI
|
12.99 Minutes
Standard Deviation 9.70
|
13.18 Minutes
Standard Deviation 7.27
|
5.34 Minutes
Standard Deviation 4.53
|
SECONDARY outcome
Timeframe: 5 minutes pre-dose, 5 minutes post-dosePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography
|
0.576 Degree Celsius
Standard Deviation 3.3539
|
-0.278 Degree Celsius
Standard Deviation 2.6927
|
-0.803 Degree Celsius
Standard Deviation 2.0125
|
SECONDARY outcome
Timeframe: 5 minutes pre-dose, 5 minutes post-dosePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI
|
-0.01 Perfusion units
Standard Deviation 74.996
|
-10.13 Perfusion units
Standard Deviation 68.037
|
-50.16 Perfusion units
Standard Deviation 65.169
|
SECONDARY outcome
Timeframe: 5 minutes pre-dose, 5 minutes post-dosePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography
|
-0.424 Degree Celsius
Standard Deviation 1.7483
|
-0.127 Degree Celsius
Standard Deviation 1.7076
|
0.332 Degree Celsius
Standard Deviation 1.5891
|
SECONDARY outcome
Timeframe: 5 minutes pre-dose, 5 minutes post-dosePopulation: 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.
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).
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI
|
3.56 Perfusion units
Standard Deviation 56.143
|
14.16 Perfusion units
Standard Deviation 57.611
|
34.86 Perfusion units
Standard Deviation 52.792
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Temanogrel 120 mg
n=13 Participants
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 Participants
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 Participants
Participants received placebo in this study.
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
TEAEs
|
4 Participants
|
3 Participants
|
6 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Temanogrel 120 mg
Temanogrel 60 mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Temanogrel 120 mg
n=13 participants at risk
Participants received temanogrel 120 mg in the study.
|
Temanogrel 60 mg
n=13 participants at risk
Participants received temanogrel 60 mg in this study.
|
Placebo
n=13 participants at risk
Participants received placebo in the study.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
23.1%
3/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Nervous system disorders
Hypoaesthesia
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Nervous system disorders
Head discomfort
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
General disorders
Oedema peripheral
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
General disorders
Peripheral swelling
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Infections and infestations
Urinary tract infection
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
0.00%
0/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
7.7%
1/13 • Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER