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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004741-24 | EudraCT Number | ||
| U1111-1201-7990 | Other Identifier | WHO |
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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.
The study will enroll approximately 366 participants. Participants will be randomly assigned to one of the two treatment groups in 1:1 ratio:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Actovegin 1200 mg | Experimental | 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. |
|
| Placebo | Placebo Comparator | Actovegin placebo-matching, intravenously, once daily for up to 2 weeks and actovegin placebo-matching tablets, orally, TID for up to 10 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Actovegin | Drug | Actovegin intravenous infusion and tablets. |
| |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center of Vascular and Heart Disease | Tbilisi | 0159 | Georgia | |||
| Aversi Clinic |
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment
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Participants with peripheral arterial occlusive disease (PAD) Fontaine stage IIB were enrolled in this study to receive either actovegin or placebo in a 1:1 ratio.
Participants took part in the study at 19 investigative sites in Russia, Kazakhstan and Georgia from 01 May 2018 to 28 August 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Actovegin placebo-matching infusion, intravenously, once daily for up to 2 weeks followed by actovegin placebo-matching tablets, orally, thrice daily for up to 10 weeks. |
| FG001 | Actovegin 1200 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 19, 2019 | Jul 30, 2020 |
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| Placebo |
| Drug |
Actovegin placebo-matching intravenous infusion and tablets. |
|
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 |
| Tbilisi |
| 0160 |
| Georgia |
| "National scientific centre of oncology and transplantology" | Astana | Z05K4F3 | Kazakhstan |
| Regional Clinic Hospital | Shymkent | X09E1G4 | Kazakhstan |
| NSHI Road clinical hospital at Chelyabinsk station of OAO RZD | Chelyabinsk | 454092 | Russia |
| Federal state budgetary research institution Research Institute for Complex Issues of Cardiovascular Diseases | Kemerovo | 650002 | Russia |
| BMH Kursk regional clinical hospital of Healthcare department of Kursk region | Kursk | 305007 | Russia |
| SBHI of Moscow city "City clinical hospital #29 n.a. N.E. Bauman of Moscow Healthcare department | Moscow | 111020 | Russia |
| SBHI of Moscow healthcare department City clinical hospital #15 n.a. O.M Filatov of Moscow healthcare department | Moscow | 111539 | Russia |
| SBHI of Moscow Research Institute of Emergency Medicine n.a. N.V. Sklifosofsky of Moscow Healthcare department | Moscow | 129090 | Russia |
| 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 | Novosibirsk | 630117 | Russia |
| BHI of Omsk region Regional clinical hospital, vessel surgery department | Omsk | 644111 | Russia |
| FSBEI HE Rostov State Medical University of MoH of Russia | Rostov-on-Don | 344022 | Russia |
| 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 | Ryazan | 390026 | Russia |
| North-Western State Medical University named after I.I. Mechnikov | Saint Petersburg | 191015 | Russia |
| SPb SBHI City multipurpose hospital #2 | Saint Petersburg | 194354 | Russia |
| Pavlov First Saint Petersburg State Medical University, Faculty surgery chair, cardio-vessel surgery department | Saint Petersburg | 197022 | Russia |
| SPb SBHI Consulting and diagnostic center #85 | Saint Petersburg | 198260 | Russia |
| State Healthcare Institution of Saratov region "Region clinical hospitai" | Saratov | 410053 | Russia |
| Municipal State Budgetary Healthcare Institution of Sochi "City hospital 4" | Sochi | 354057 | Russia |
Actovegin 1200 milligram (mg), infusion, intravenously, once daily for up to 2 weeks followed by actovegin 200 mg, tablets, orally, thrice daily (1200 mg/day) for up to 10 weeks.
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| NOT COMPLETED |
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The safety set included all participants who were randomized and received at least 1 dose of double-blind study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Actovegin placebo-matching infusion, intravenously, once daily for up to 2 weeks followed by actovegin placebo-matching tablets, orally, thrice daily for up to 10 weeks. |
| BG001 | Actovegin 1200 mg | Actovegin 1200 mg, infusion, intravenously, once daily for up to 2 weeks followed by actovegin 200 mg, tablets, orally, thrice daily (1200 mg/day) for up to 10 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | centimeter (cm) |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kilogram (Kg) |
| |||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
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| PAD Stage II Duration | Mean | Standard Deviation | years |
| |||||||||||||||
| Diabetic Status | Count of Participants | Participants |
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| Location of the Lesion | Count of Participants | Participants |
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| Ankle Brachial Index (ABI) at Bilateral (BL) | The ABI assessment was performed by measuring the systolic blood pressure (sBP) from both brachial arteries, posterior tibial arteries, and both dorsalis pedis arteries. ABI was calculated as ankle sBP divided by brachial sBP. Ankle sBP was the higher of two systolic blood pressures from a lower limb. Brachial sBP was the higher of systolic blood pressures from both upper limbs. | Mean | Standard Deviation | ratio |
| ||||||||||||||
| Smoking Status | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The full analysis set (FAS) included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Error | percent change | Baseline up to Week 12 |
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| Secondary | 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. | The FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. Participants evaluable for this measure at given time point were included for the assessment. | Posted | Least Squares Mean | Standard Error | percent change | Baseline up to Weeks 2 and 24 |
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| Secondary | 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. | The FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. Participants evaluable for this measure at given time point were included for the assessment. | Posted | Mean | Standard Deviation | meter | Baseline, Weeks 2, 12 and 24 |
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| Secondary | 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. | The FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. Participants evaluable for this measure at given time point were included for the assessment. | Posted | Number | percentage of participants | Weeks 12 and 24 |
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| Secondary | 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. | The FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. | Posted | Number | percentage of participants | Week 24 |
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| Secondary | 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. | The FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary endpoint. Participants evaluable for this measure at given time point were included for the assessment. | Posted | Mean | Standard Deviation | points on a scale | Baseline, Weeks 12 and 24 |
|
Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug up to Day 168
At each visit the investigator had to assess any occurrence of adverse events. Participants may report adverse events occurring at any other time during the study. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Actovegin placebo-matching infusion, intravenously, once daily for up to 2 weeks followed by actovegin placebo-matching tablets, orally, thrice daily for up to 10 weeks. | 0 | 182 | 3 | 182 | 20 | 182 |
| EG001 | Actovegin 1200 mg | Actovegin 1200 mg, infusion, intravenously, once daily for up to 2 weeks followed by actovegin 200 mg, tablets, orally, thrice daily (1200 mg/day) for up to 10 weeks. | 0 | 184 | 9 | 184 | 23 | 184 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
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| Gangrene | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Arterial bypass thrombosis | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Haemorrhagic stroke | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Peripheral artery occlusion | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Extremity necrosis | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Carbohydrate metabolism disorder | Congenital, familial and genetic disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (22.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pyelonephritis chronic | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Anal abscess | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Chronic hepatitis C | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Paronychia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Respiratory tract infection viral | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Ear injury | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Shunt thrombosis | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Wound | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA (22.0) | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
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| Osteochondrosis | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cerebral arteriosclerosis | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Leukocyturia | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
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| Peripheral arterial occlusive disease | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
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The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 11, 2019 | Jul 30, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
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| ID | Term |
|---|---|
| C015646 | Actovegin |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Kazakhstan |
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| Georgia |
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| Non-diabetic |
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| Femoro-popliteal segment |
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| Both segments |
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| Former smoker |
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| Never-smoked. |
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| Units |
|---|
| Counts |
|---|
| Participants |
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Actovegin 1200 mg, infusion, intravenously, once daily for up to 2 weeks followed by actovegin 200 mg, tablets, orally, thrice daily (1200 mg/day) for up to 10 weeks.
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