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

Primary Purpose

Peripheral Arterial Diseases

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Actovegin

Placebo

About this trial

This is an interventional treatment trial for Peripheral Arterial Diseases focused on measuring Drug Therapy

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Center of Vascular and Heart Disease
Aversi Clinic
"National scientific centre of oncology and transplantology"
Regional Clinic Hospital
NSHI Road clinical hospital at Chelyabinsk station of OAO RZD
Federal state budgetary research institution Research Institute for Complex Issues of Cardiovascular Diseases
BMH Kursk regional clinical hospital of Healthcare department of Kursk region
SBHI of Moscow city "City clinical hospital #29 n.a. N.E. Bauman of Moscow Healthcare department
SBHI of Moscow healthcare department City clinical hospital #15 n.a. O.M Filatov of Moscow healthcare department
SBHI of Moscow Research Institute of Emergency Medicine n.a. N.V. Sklifosofsky of Moscow Healthcare department
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
BHI of Omsk region Regional clinical hospital, vessel surgery department
FSBEI HE Rostov State Medical University of MoH of 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
Pavlov First Saint Petersburg State Medical University, Faculty surgery chair, cardio-vessel surgery department
SPb SBHI Consulting and diagnostic center #85
North-Western State Medical University named after I.I. Mechnikov
SPb SBHI City multipurpose hospital #2
State Healthcare Institution of Saratov region "Region clinical hospitai"
Municipal State Budgetary Healthcare Institution of Sochi "City hospital 4"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Actovegin 1200 mg

Placebo

Arm Description

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.

Actovegin placebo-matching, intravenously, once daily for up to 2 weeks and actovegin placebo-matching tablets, orally, TID for up to 10 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percent Change From Baseline in ICD at 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.

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.

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.

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.

Full Information

NCT ID

NCT03469349

First Posted

March 13, 2018

Last Updated

October 2, 2020

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03469349

Brief Title

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

Acronym

APOLLO

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

May 1, 2018 (Actual)

Primary Completion Date

May 28, 2019 (Actual)

Study Completion Date

August 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Arterial Diseases

Keywords

Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

366 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Actovegin 1200 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Actovegin placebo-matching, intravenously, once daily for up to 2 weeks and actovegin placebo-matching tablets, orally, TID for up to 10 weeks.

Intervention Type

Drug

Intervention Name(s)

Actovegin

Intervention Description

Actovegin intravenous infusion and tablets.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Actovegin placebo-matching intravenous infusion and tablets.

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Initial Claudication Distance (ICD) at Week 12

Description

Time Frame

Baseline up to Week 12

Secondary Outcome Measure Information:

Title

Percent Change From Baseline in ICD at Weeks 2 and 24

Description

Time Frame

Baseline up to Weeks 2 and 24

Title

Absolute Change From Baseline in Absolute Claudication Distance (ACD) at Weeks 2, 12 and 24

Description

Time Frame

Baseline, Weeks 2, 12 and 24

Title

Percentage of Participants With Rest Pain at Weeks 12 and 24

Description

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.

Time Frame

Weeks 12 and 24

Title

Percentage of Participants With Revascularization Procedures at Week 24

Description

Time Frame

Week 24

Title

Change From Baseline in 36-Item Short Form Survey (SF-36) at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Center of Vascular and Heart Disease

City

Tbilisi

ZIP/Postal Code

0159

Country

Georgia

Facility Name

Aversi Clinic

City

Tbilisi

ZIP/Postal Code

0160

Country

Georgia

Facility Name

"National scientific centre of oncology and transplantology"

City

Astana

ZIP/Postal Code

Z05K4F3

Country

Kazakhstan

Facility Name

Regional Clinic Hospital

City

Shymkent

ZIP/Postal Code

X09E1G4

Country

Kazakhstan

Facility Name

NSHI Road clinical hospital at Chelyabinsk station of OAO RZD

City

Chelyabinsk

ZIP/Postal Code

454092

Country

Russian Federation

Facility Name

Federal state budgetary research institution Research Institute for Complex Issues of Cardiovascular Diseases

City

Kemerovo

ZIP/Postal Code

650002

Country

Russian Federation

Facility Name

BMH Kursk regional clinical hospital of Healthcare department of Kursk region

City

Kursk

ZIP/Postal Code

305007

Country

Russian Federation

Facility Name

SBHI of Moscow city "City clinical hospital #29 n.a. N.E. Bauman of Moscow Healthcare department

City

Moscow

ZIP/Postal Code

111020

Country

Russian Federation

Facility Name

SBHI of Moscow healthcare department City clinical hospital #15 n.a. O.M Filatov of Moscow healthcare department

City

Moscow

ZIP/Postal Code

111539

Country

Russian Federation

Facility Name

SBHI of Moscow Research Institute of Emergency Medicine n.a. N.V. Sklifosofsky of Moscow Healthcare department

City

Moscow

ZIP/Postal Code

129090

Country

Russian Federation

Facility Name

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

Novosibirsk

ZIP/Postal Code

630117

Country

Russian Federation

Facility Name

BHI of Omsk region Regional clinical hospital, vessel surgery department

City

Omsk

ZIP/Postal Code

644111

Country

Russian Federation

Facility Name

FSBEI HE Rostov State Medical University of MoH of Russia

City

Rostov-on-Don

ZIP/Postal Code

344022

Country

Russian Federation

Facility Name

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

Ryazan

ZIP/Postal Code

390026

Country

Russian Federation

Facility Name

Pavlov First Saint Petersburg State Medical University, Faculty surgery chair, cardio-vessel surgery department

City

Saint Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

SPb SBHI Consulting and diagnostic center #85

City

Saint Petersburg

ZIP/Postal Code

198260

Country

Russian Federation

Facility Name

North-Western State Medical University named after I.I. Mechnikov

City

Saint-Petersburg

ZIP/Postal Code

191015

Country

Russian Federation

Facility Name

SPb SBHI City multipurpose hospital #2

City

Saint-Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

Facility Name

State Healthcare Institution of Saratov region "Region clinical hospitai"

City

Saratov

ZIP/Postal Code

410053

Country

Russian Federation

Facility Name

Municipal State Budgetary Healthcare Institution of Sochi "City hospital 4"

City

Sochi

ZIP/Postal Code

354057

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

Learn more about this trial

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

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