Clinical trial NCT03469349: Actovegin 12-Week Treatment Given First Intravenously and Subsequently Orally in Participants With Peripheral Arterial Occlusive Disease Fontaine Stage IIB
Official title: A Randomized, International, Multicenter, Parallel Group, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Actovegin 12-Week Treatment Given First Intravenously and Subsequently Orally in Subjects With Peripheral Arterial Occlusive Disease Fontaine Stage IIB
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peripheral Arterial Diseases
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-03-19
Enrollment: 366
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and safety of actovegin in participants with peripheral arterial disease (PAD) Fontaine Stage IIB.

Detailed description: The study will enroll approximately 366 participants. Participants will be randomly assigned to one of the two treatment groups in 1:1 ratio:

1. Actovegin
2. Placebo (dummy inactive substance) - this is a tablet/intravenous infusion that looks like the study drug but has no active ingredient

All participants will be asked to take intravenous infusion for 2 weeks followed by oral tablets for 10 weeks.

This multi-center trial will be conducted Russia, Georgia, and Kazakhstan. The overall time to participate in this study is 25 to 26 weeks. Participants will make multiple visits to the clinic, and 12 weeks after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Has a history of stable intermittent claudication lasting more than 6 months before Screening.
2. Has a diagnosis of peripheral arterial disease (PAD) (Code I70.2 according to the international classification of diseases-10th revision) Fontaine Stage IIB confirmed by ultrasound color duplex imaging.
3. Has a resting Doppler ankle-brachial index of less than or equal to (\<=) 0.9.
4. Has intermittent claudication with initial claudication distance (ICD) less than (\<) 200 meters.
5. Is not newly diagnosed with PAD and has a history of stable PAD therapy for at least 2 weeks before Screening.

Exclusion Criteria:

1. Has PAD Fontaine Stage III or IV (pain at rest, non-healing ulceration, or gangrene).
2. Has evidence of nonatherosclerotic PAD.
3. Has greater than (\>) 25 percent (%) variability in absolute claudication distance (ACD) based on treadmill testing during the screening period.
4. Has lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within 3 months before Screening.
5. Is eligible for surgical/interventional reconstruction.
6. Had a myocardial infarction or major cardiac surgery within 3 months before Screening.
7. Has congestive heart failure (New York Heart Association Class III/IV).
8. Has uncontrolled diabetes mellitus (glycosylated hemoglobin \[HbA1c \>9%\]) or diabetic polyneuropathy.
9. Has any other illness that significantly limits exercise capacity or other medical condition, including any psychiatric disorder that limits participation (in the judgement of the investigator).
10. The subject has received any prohibited medication within 14 days before Randomization (Day 1)
11. The subject is undergoing the supervised exercise training program by the time of Screening and is going to continue this program due to its effectiveness.

Primary outcomes:
measure: Percent Change From Baseline in Initial Claudication Distance (ICD) at Week 12
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Percent Change From Baseline in ICD at Weeks 2 and 24
timeFrame: Baseline up to Weeks 2 and 24
measure: Absolute Change From Baseline in Absolute Claudication Distance (ACD) at Weeks 2, 12 and 24
timeFrame: Baseline, Weeks 2, 12 and 24
measure: Percentage of Participants With Rest Pain at Weeks 12 and 24
timeFrame: Weeks 12 and 24
measure: Percentage of Participants With Revascularization Procedures at Week 24
timeFrame: Week 24
measure: Change From Baseline in 36-Item Short Form Survey (SF-36) at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Center of Vascular and Heart Disease
city: Tbilisi
country: Georgia
facility: Aversi Clinic
city: Astana
country: Kazakhstan
facility: "National scientific centre of oncology and transplantology"
city: Shymkent
country: Kazakhstan
facility: Regional Clinic Hospital
city: Chelyabinsk
country: Russian Federation
facility: NSHI Road clinical hospital at Chelyabinsk station of OAO RZD
city: Kemerovo
country: Russian Federation
facility: Federal state budgetary research institution Research Institute for Complex Issues of Cardiovascular Diseases
city: Kursk
country: Russian Federation
facility: BMH Kursk regional clinical hospital of Healthcare department of Kursk region
city: Moscow
country: Russian Federation
facility: SBHI of Moscow city "City clinical hospital #29 n.a. N.E. Bauman of Moscow Healthcare department
city: Moscow
country: Russian Federation
facility: SBHI of Moscow healthcare department City clinical hospital #15 n.a. O.M Filatov of Moscow healthcare department
city: Moscow
country: Russian Federation
facility: SBHI of Moscow Research Institute of Emergency Medicine n.a. N.V. Sklifosofsky of Moscow Healthcare department
city: Novosibirsk
country: Russian Federation
facility: Scientific Research Institute of Clinical and Experimental Lymphology - a branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Regional clinical hospital, vessel surgery department
city: Rostov-on-Don
country: Russian Federation
facility: FSBEI HE Rostov State Medical University of MoH of Russia
city: Ryazan
country: Russian Federation
facility: SBHI of Ryazan region Regional clinical cardiological dispensary, vessel surgery department/ FSBI of Ryazan Region "Ryazan State Medical Univesity n.a. I.P. Pavlov" of MoH of Russia
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University, Faculty surgery chair, cardio-vessel surgery department
city: Saint Petersburg
country: Russian Federation
facility: SPb SBHI Consulting and diagnostic center #85
city: Saint-Petersburg
country: Russian Federation
facility: North-Western State Medical University named after I.I. Mechnikov
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBHI City multipurpose hospital #2
city: Saratov
country: Russian Federation
facility: State Healthcare Institution of Saratov region "Region clinical hospitai"
city: Sochi
country: Russian Federation
facility: Municipal State Budgetary Healthcare Institution of Sochi "City hospital 4"
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: