Trial Outcomes & Findings for Efficacy Study of PDE-5 Inhibitor and Calcium Channel Inhibitor for the Treatment of Secondary Raynaud Phenomenon (NCT NCT01280266)

NCT ID: NCT01280266

Last Updated: 2012-12-11

Results Overview

Change in RP frequency after amlodipine and udenafil number of RP attack per day 0 -- unlimited.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 29 participants
• Primary outcome timeframe: baselin and 4 weeks
• Results posted on: 2012-12-11

Participant Flow

Recruitment begin Jan 13 2011 until Mar 15 2011. Location: Rheumatology outpatient clinic at Seoul National University Hospital, Seoul, Korea.

30 Patients were initially recruited, but an error occurred in obtaining informed consent and this one was withdrawn.

Participant milestones

Measure	Amlodipine-Udenafil (AU) Arm Amlodipine 10mg PO QD for 4 weeks, washout period for 1week, then Udenafil 100mg PO QD for 4 weeks.	Udenafil-Amlodipine (UA) Arm Udenafil 100mg PO QD for 4 weeks, washout period for 1 week, then Udenafil 10mg PO QD for 4 weeks.
First Intervention (Week 1-4) STARTED	15	14
First Intervention (Week 1-4) COMPLETED	14	12
First Intervention (Week 1-4) NOT COMPLETED	1	2
Washout Period (Week 4-5) STARTED	14	12
Washout Period (Week 4-5) COMPLETED	14	12
Washout Period (Week 4-5) NOT COMPLETED	0	0
Second Intervention (Week 5-9) STARTED	14	12
Second Intervention (Week 5-9) COMPLETED	14	12
Second Intervention (Week 5-9) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Amlodipine-Udenafil (AU) Arm Amlodipine 10mg PO QD for 4 weeks, washout period for 1week, then Udenafil 100mg PO QD for 4 weeks.	Udenafil-Amlodipine (UA) Arm Udenafil 100mg PO QD for 4 weeks, washout period for 1 week, then Udenafil 10mg PO QD for 4 weeks.
First Intervention (Week 1-4) Adverse Event	1	0
First Intervention (Week 1-4) Withdrawal by Subject	0	2

Baseline Characteristics

Efficacy Study of PDE-5 Inhibitor and Calcium Channel Inhibitor for the Treatment of Secondary Raynaud Phenomenon

Baseline characteristics by cohort

Measure	Amlodipine-Udenafil (AU) Arm n=14 Participants Amlodipine first, then Udenafil	Udenafil-Amlodipine (UA) Arm n=12 Participants Udenafil first, then Amlodipine	Total n=26 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
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	49.6 years STANDARD_DEVIATION 14.0 • n=5 Participants	52.3 years STANDARD_DEVIATION 10.3 • n=7 Participants	50.9 years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Korea, Republic of	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants
Disease subtype Localized systemic sclerosis (SSc)	1 participant n=5 Participants	2 participant n=7 Participants	3 participant n=5 Participants
Disease subtype diffuse SSc	10 participant n=5 Participants	7 participant n=7 Participants	17 participant n=5 Participants
Disease subtype Mixed connective tissue disease	1 participant n=5 Participants	2 participant n=7 Participants	3 participant n=5 Participants
Disease subtype Sjogren's disease	2 participant n=5 Participants	1 participant n=7 Participants	3 participant n=5 Participants
RP duration	8.8 years STANDARD_DEVIATION 8.7 • n=5 Participants	5.6 years STANDARD_DEVIATION 2.3 • n=7 Participants	7.3 years STANDARD_DEVIATION 6.6 • n=5 Participants
Prior use of vasodilator calcium channel blocker	1 Participant n=5 Participants	4 Participant n=7 Participants	5 Participant n=5 Participants
Prior use of vasodilator angiotensin receptor blocker	2 Participant n=5 Participants	0 Participant n=7 Participants	2 Participant n=5 Participants
Prior use of vasodilator Pentyxifylline	1 Participant n=5 Participants	1 Participant n=7 Participants	2 Participant n=5 Participants
Prior use of vasodilator No prior use	10 Participant n=5 Participants	7 Participant n=7 Participants	17 Participant n=5 Participants

PRIMARY outcome

Timeframe: baselin and 4 weeks

Population: 14 patients in UA arm + 12 patients in AU arm

Change in RP frequency after amlodipine and udenafil number of RP attack per day 0 -- unlimited.

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
RP Attacks Per Day	-0.5 attacks per day Standard Deviation 1.4	-0.5 attacks per day Standard Deviation 0.9

SECONDARY outcome

Timeframe: baseline and 4 weeks

change in the RCS. RCS combines daily activty, frequency, duration and severity as well as impact of RP attack (Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon, Merkel et al,Arthritis Rheum. 2002 Sep;46(9):2410-20).

Range 0-10 ordinal scale 0..good 10.. bad

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in Raynaud's Condition Score (RCS)	-0.5 units on a scale Standard Deviation 1.5	-0.3 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: baseline and 4 weeks

Change in the average RP duration in minutes (min) per attack. 0 -- unlimited

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in the RP Duration	-1.1 min per attack Standard Deviation 5.9	-1.4 min per attack Standard Deviation 11.4

SECONDARY outcome

Timeframe: 0 and 4 weeks

Ordinal scale 0-10 0 good 10 bad

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in Health Assessment Questionnaire (HAQ)	0.1 units on a scale Standard Deviation 0.4	-0.1 units on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: at 0 (baseline) and 4 weeks (after treatment)

Physician's global assessment (PGA) on VAS assesses the overall condition of the patient. The scale ranges from 0 - 10, with 0 being good and 10 bad. As such, change in the GPA measures the change in the patient's condition from the baseline.

negative value (decrease in value) means improvement.

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in Physician's Global Assessment on Visual Analogue Scale (VAS)	-0.9 units on a scale Standard Deviation 1.4	-1.5 units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: baseline and 4 weeks

0 - unlimited. Number of digital ulcers in all fingers are counted by the investigators and recorded at each visit. The number of ulcers in all fingers indirectly reflect the extent of critical ischemia. As such. the decrease in digital ulcer number reflects positive response to treatment (=better blood flow), whereas the increase ulcer numbers indicates worsening finger ischemia from baseline.

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in Digital Ulcer Number	0.1 Digital ulcers Standard Deviation 0.4	0.1 Digital ulcers Standard Deviation 0.3

SECONDARY outcome

Timeframe: baseline and 4 weeks

Change in digital artery flow velocity in proper palmar digital artery in cm/sec.

0-unlimited

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Change in Peak Systolic Flow (cm/Sec)	-19.9 cm/sec Standard Deviation 145.9	63.2 cm/sec Standard Deviation 170.2

SECONDARY outcome

Timeframe: baseline and 4 weeks

changes in the averaged blood flow (Time-averaged peak velocity) Blood flow in cm/sec 0 - unlimited.

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Time-averaged Peak Velocity (cm/Sec)	-17.3 cm/sec Standard Deviation 98.6	33.4 cm/sec Standard Deviation 123

SECONDARY outcome

Timeframe: baseline and 4 weeks

The temperature difference between finger tips and dorsum of same hand. range 0 - unlimited in degree celcius.

Outcome measures

Measure	Amlodipine n=26 Participants Changes in RP attacks per day during amlodipine 10 mg orally per day	Udenafil n=26 Participants Changes in RP attacks per day during udenafil 100mg orally per day
Dorsal-digital-difference.	-0.7 degree celcius. Standard Deviation 3.2	-1.4 degree celcius. Standard Deviation 3.3

Adverse Events

Amlodipine

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Udenafil

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Amlodipine n=26 participants at risk Adverse effects observed while taking amlodipine in both study arms	Udenafil n=26 participants at risk Adverse effects observed while taking udenafil in both study arms
General disorders Facial edema	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.

Other adverse events

Measure	Amlodipine n=26 participants at risk Adverse effects observed while taking amlodipine in both study arms	Udenafil n=26 participants at risk Adverse effects observed while taking udenafil in both study arms
General disorders Facial flushing	30.8% 8/26 • Number of events 8 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	50.0% 13/26 • Number of events 13 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Facial edema	15.4% 4/26 • Number of events 4 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	38.5% 10/26 • Number of events 10 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Peripheral edema	15.4% 4/26 • Number of events 4 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	23.1% 6/26 • Number of events 6 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Headache	11.5% 3/26 • Number of events 3 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	11.5% 3/26 • Number of events 3 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
Eye disorders Blurred vision	7.7% 2/26 • Number of events 2 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	7.7% 2/26 • Number of events 2 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
Nervous system disorders Paresthesia	11.5% 3/26 • Number of events 3 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
Skin and subcutaneous tissue disorders Pruritus	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	7.7% 2/26 • Number of events 2 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Epistaxis	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Dry mouth	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
General disorders Throat irritation	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.
Congenital, familial and genetic disorders Zoster	3.8% 1/26 • Number of events 1 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.	0.00% 0/26 • During 8 weeks while taking a study drug. As a cross over trial, study participants received both amlodipine and udenafil following each other.

Additional Information

Dr. Eun Bong Lee

Seoul National University

Phone: +82 2 2072-3944

Email: leb7616@snu.ac.kr

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place