Actovegin 12-Week Treatment Given First Intravenously and Subsequently Orally in Participants With Peripheral Arterial Occlusive Disease Fontaine Stage IIB

Study Overview
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Brief Summary
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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
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The study will enroll approximately 366 participants. Participants will be randomly assigned to one of the two treatment groups in 1:1 ratio: Actovegin 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.

Official Title
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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

Conditions
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Peripheral Arterial Diseases

Intervention / Treatment
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* Drug: Actovegin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a history of stable intermittent claudication lasting more than 6 months before Screening. 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. Has a resting Doppler ankle-brachial index of less than or equal to (<=) 0.9. Has intermittent claudication with initial claudication distance (ICD) less than (<) 200 meters. Is not newly diagnosed with PAD and has a history of stable PAD therapy for at least 2 weeks before Screening. Exclusion Criteria: Has PAD Fontaine Stage III or IV (pain at rest, non-healing ulceration, or gangrene). Has evidence of nonatherosclerotic PAD. Has greater than (>) 25 percent (%) variability in absolute claudication distance (ACD) based on treadmill testing during the screening period. Has lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within 3 months before Screening. Is eligible for surgical/interventional reconstruction. Had a myocardial infarction or major cardiac surgery within 3 months before Screening. Has congestive heart failure (New York Heart Association Class III/IV). Has uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c >9%]) or diabetic polyneuropathy. 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). The subject has received any prohibited medication within 14 days before Randomization (Day 1) 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Actovegin 1200 mg<br>Actovegin 1200 milligram (mg), intravenously, once daily for up to 2 weeks followed by actovegin 200 mg, tablets, orally, thrice daily (TID) (1200 mg/day) for up to 10 weeks. | Drug: Actovegin<br>* Actovegin intravenous infusion and tablets.<br>|
| Placebo Comparator: Placebo<br>Actovegin placebo-matching, intravenously, once daily for up to 2 weeks and actovegin placebo-matching tablets, orally, TID for up to 10 weeks. | Drug: Placebo<br>* Actovegin placebo-matching intravenous infusion and tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Initial Claudication Distance (ICD) at Week 12 | ICD was the distance walked at the onset of claudication pain or pain-free walking distance. ICD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 kilometer per hour (km/h) with a 10 percent (%) grade. | Baseline up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in ICD at Weeks 2 and 24 | ICD was the distance walked at the onset of claudication pain or pain-free walking distance. ICD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 km/h with a 10% grade. | Baseline up to Weeks 2 and 24 | 
| Absolute Change From Baseline in Absolute Claudication Distance (ACD) at Weeks 2, 12 and 24 | ACD was the distance at which claudication pain becomes so severe that the participant was forced to stop, also known as maximal walking distance. ACD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 km/h with a 10% grade. The investigator will record the distance from walking start to the point where the participant is unable to walk anymore. | Baseline, Weeks 2, 12 and 24 | 
| Percentage of Participants With Rest Pain at Weeks 12 and 24 | Rest pain was defined as a continuous burning pain, that begins, or is aggravated, after reclining or elevating the limb and is relieved by sitting or standing. | Weeks 12 and 24 | 
| Percentage of Participants With Revascularization Procedures at Week 24 | Revascularization was defined by a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3 following use of the Penumbra System. TIMI scores were used to describe blood flow at the treated vessel with 0 designating no flow and 3 for normal flow. | Week 24 | 
| Change From Baseline in 36-Item Short Form Survey (SF-36) at Weeks 12 and 24 | The SF-36 was a questionnaire that evaluated a participant's health related quality of life. SF-36 included 36 questions related to 8 health dimensions: physical functioning, role-physical (role limitations due to physical health problems), bodily pain, general health, vitality (energy/fatigue), social functioning, role-emotional (role limitations due to emotional problems), and mental health. Based on these 4 scales (physical functioning, role-physical, bodily pain, general health), the physical health score was generated which ranges between 0 and 100, with higher scores indicating a better quality of life. Based on these 4 scales (vitality, social functioning, role-emotional, and mental health), the mental health score was generated which ranges between 0 and 100, with higher scores indicating a better quality of life. | Baseline, Weeks 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy