Critical Limb Ischemia
Conditions
Keywords
lower leg ischemia, peripheral artery disease
Brief summary
The purpose of this study is to determine the safety, tolerability and preliminary efficacy of intramuscular injections of VM202 for subjects with critical limb ischemia. Subjects selected for this study will have critical limb ischemia that has not responded to standard therapy with symptoms including pain at rest and/or ischemic ulcers.
Detailed description
The study will consist of four (4) cohorts with a total of 3 subjects enrolled in each cohort to VM202.For each dose cohort, VM202 will be administered as a local intramuscular injection in 2 divided doses with a 2-week interval between the injections. Preliminary efficacy (hemodynamic assessments), safety and tolerability will be evaluated at Baseline (screening) and at designated time points throughout the study. After the first subject in each cohort completed Day 30 (±2 days), and before the Day 15 dosing of the other 2 subjects in the same cohort, an interim safety evaluation was performed with the submission of safety data to the Data Safety Monitoring Committee. All four dose cohorts will be followed for up to 5 years from the time of the first dose of study drug administration.
Interventions
BIOLOGICALVM202 2 mg
2 mg intramuscular injection with the first half of the total dose given on Day 1 and the second half on Day 15
BIOLOGICALVM202 4 mg
4 mg intramuscular injection, with half of the total dose given on Day 1 and the second half given on Day 15
BIOLOGICALVM202 8 mg
8 mg intramuscular injection. The first half of the total dose given on Day 1 and the second half on Day 15.
BIOLOGICALVM202 16 mg
16 mg dose intramuscular injection. The first half of the total dose given on Day 1 and the second half on Day 15.
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, between 20 and 90 years of age * Have critical limb ischemia (Rutherford Class 4 and 5) and considered not a candidate for bypass graft surgery or percutaneous angioplasty due to co-morbid conditions, failure of previous surgical or interventional procedures or caliber of grafting arteries. Critical Limb ischemia is defined as 1. Stable symptoms on standard therapy including anti-platelet agents, vascular rheologic agents, cilostazol, anticoagulant and pain medication for 30 days. 2. Pain at rest and/or ischemic ulcers for a minimum of 4 weeks. * Have diagnostic angiography of the affected limb in the last 12 months demonstrating a significant occlusion of one more of the following arteries: iliac, superficial femoral, popliteal, and one or more infra-popliteal arteries. * Have a resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of less than or equal to 60mmHg or a resting toe systolic pressure of less than or equal to 40 mmHg in the affected limb. * Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study including anti-platelet and statin inhibitor treatment * Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures * Women who are surgically sterile or at least 1 year postmenopausal or who have been practicing adequate contraception for at least 12 weeks prior to entering the study. If the subject is of child-bearing potential, she must have a negative serum pregnancy test result prior to study enrollment and must agree to repeat pregnancy screening tests during the study * If the subject or the subject's partner(s) is of child bearing potential, the subject and the subject's partner(s) must agree to use a double barrier method of birth control while participating in this study.
Exclusion criteria
* Subjects who have undergone a revascularization procedure or sympathectomy within 12 weeks prior to study entry that remains patent. A failed revascularization procedure in the previous 4 weeks is acceptable. * Subjects with grade 3 (hemorrhages, exudates) or grade 4 (papilledema) retinopathy. * Subjects currently receiving immunosuppressive medications, chemotherapy, radiation therapy. * Subject with aorta-iliac occlusion (greater than 75%). * Subjects that will require amputation within 4 weeks of randomization. * Subjects with any co-morbid conditions likely to interfere with assessment of safety or efficacy or with an estimated life expectancy of less than 6 months * Subjects with history of drug (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 3 months. * Subjects with a current history or new screening finding of malignant neoplasm except for basal cell carcinoma of the skin and squamous cell carcinoma of the skin (if excised and no evidence of recurrence). * Subjects with evidence of active infection (e.g. cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the extremity planned for treatment. * Subjects with a clinically significant abnormality in routine hematology, urinalysis, chemistry, liver function or other laboratory tests, including HIV, Hepatitis B, Cytomegalovirus, hepatitis C virus, Venereal Disease Research Laboratory test, prostate-specific antigen, and chorio-embryonic antigen, or signs of malignant neoplasm by radiological imaging tests, including chest radiography at Screening or Day 1. Specific laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events. | Day 1 to Day 365 | Treatment-emergent adverse events defined as adverse events after the first dose of Engensis (Day 1) through Day 365 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pain Visual Analog Scale | Days 15, 28, 59, 91, 180, and 365 | Pain intensity was assessed by subjects marking a place on a 100 mm Visual Analog Scale ranging from 0 = no pain to 100 = worst possible pain. The distance from 0 to the mark was to be measured in millimeters (0 to 100 mm). |
| Change From Baseline in Ankle Brachial Index | Days 15, 28, 59, 91, 180, and 365 | The Ankle Brachial Index is the ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the upper arm (brachial). Outcome measure is the Change in Baseline from Day 0 (Baseline) to Actual visit Days (Days 15, 28, 59, 91, 180 and 365). |
| Change From Baseline in Toe Brachial Index | Baseline and Days 1,15,28,59,91,180,and 365 | Toe brachial index is the ratio of the systolic blood pressure of the toes to the systolic blood pressure in the upper arm (brachial). Outcome measure is the Change in Ratio for Baseline from Day 0 (Baseline) to Actual visit Days (Days 15, 28, 59, 91, 180 and 365). |
| Change From Baseline in Transcutaneous Oxygen Pressure | Days 1 to 365 | At Screening, transcutaneous oxygen pressure was measured at pre-defined locations on the anterior and posterior calf and dorsum of the foot. The limb/chest Transcutaneous Oxygen Pressure index was calculated by using the lower of the distal limb measurements |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Engensis 2 mg (VM202). The 2 mg intramuscular injection was given on Day 1 (first half of the total dose) and Day 15 (the second half of the total dose) | 3 |
| Cohort 2 Engensis 4 mg (VM202). The 4 mg intramuscular injection was given on Day 1 (first half of the total dose) and Day 15 (the second half of the total dose) | 3 |
| Cohort 3 Engensis 8 mg (VM202). The 8 mg intramuscular injection was given on Day 1 (first half of the total dose) and Day 15 (the second half of the total dose) | 3 |
| Cohort 4 Engensis 16 mg (VM202). The 16 mg intramuscular injection was given on Day 1 (first half of the total dose) and Day 15 (the second half of the total dose) | 3 |
| Total | 12 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 4 | Cohort 3 | Cohort 2 |
|---|---|---|---|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 15.1 | 67.8 years STANDARD_DEVIATION 12.6 | 63.7 years STANDARD_DEVIATION 20.8 | 70.3 years STANDARD_DEVIATION 9 | 70.0 years STANDARD_DEVIATION 5.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 11 Participants | 3 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 12 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 1 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 3 / 3 | 0 / 3 |
Outcome results
Primary
Treatment-Emergent Adverse Events.
Treatment-emergent adverse events defined as adverse events after the first dose of Engensis (Day 1) through Day 365
Time frame: Day 1 to Day 365
Population: Safety population included all subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Treatment-Emergent Adverse Events. | Wheezing | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Skin ulcer | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Pruritus | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Gastrointestinal Disorders | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Small cell lung cancer stage unspecified | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Erythema | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Skin and Subcutaneous Tissue Disorders | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Gastric ulcer | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Musculoskeletal pain | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Prostatic specific antigen increased | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | International normalized ratio increased | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Ileus | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Muscle spasms | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Glucose urine present | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Blood glucose increased | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Investigations | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Vascular Disorders | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Blood creatinine increased | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Rhonchi | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Pain in extremity | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Musculoskeletal and Connective Tissue Disorders | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Peripheral arterial occlusive disease | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Subjects with at least one TEAE | 3 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Pyrexia | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Injection site bruising | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Haematoma | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Metastases to liver | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Chest pain | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | General Disorders and Administration Site Conditions | 2 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Hypotension | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Colon cancer | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Wound infection | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Chronic sinusitis | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Blood and Lymphatic System Disorders | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Throat irritation | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Cellulitis | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Upper respiratory infection | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Anaemia | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Respiratory, Thoracic and Mediastinal Disorders | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Urinary tract infection | 2 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Infections and Infestations | 2 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Cardiac Disorders | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Biliary adenoma | 0 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Confusional state | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Psychiatric Disorders | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Bundle branch block left | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Tongue injury | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Injury, Poisoning and Procedural Complications | 1 Participants |
| Cohort 1 | Treatment-Emergent Adverse Events. | Cyanosis | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Confusional state | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Respiratory, Thoracic and Mediastinal Disorders | 2 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Rhonchi | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Throat irritation | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Wheezing | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Vascular Disorders | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Peripheral arterial occlusive disease | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Haematoma | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Hypotension | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Blood and Lymphatic System Disorders | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Anaemia | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Cardiac Disorders | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Bundle branch block left | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Cyanosis | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Gastrointestinal Disorders | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Gastric ulcer | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Ileus | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Investigations | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Blood creatinine increased | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Blood glucose increased | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Glucose urine present | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | International normalized ratio increased | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Prostatic specific antigen increased | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Skin and Subcutaneous Tissue Disorders | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Erythema | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Pruritus | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Skin ulcer | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Injury, Poisoning and Procedural Complications | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Tongue injury | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Psychiatric Disorders | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Subjects with at least one TEAE | 3 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Infections and Infestations | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Urinary tract infection | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Upper respiratory infection | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Cellulitis | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Chronic sinusitis | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Wound infection | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | General Disorders and Administration Site Conditions | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Chest pain | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Injection site bruising | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Pyrexia | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Pain in extremity | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Muscle spasms | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Musculoskeletal pain | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Biliary adenoma | 1 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Colon cancer | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Metastases to liver | 0 Participants |
| Cohort 2 | Treatment-Emergent Adverse Events. | Small cell lung cancer stage unspecified | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Pruritus | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Cyanosis | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Skin ulcer | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Injury, Poisoning and Procedural Complications | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Bundle branch block left | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Small cell lung cancer stage unspecified | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Tongue injury | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Psychiatric Disorders | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Cardiac Disorders | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Confusional state | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Subjects with at least one TEAE | 3 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Throat irritation | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Infections and Infestations | 3 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Anaemia | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Urinary tract infection | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Biliary adenoma | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Upper respiratory infection | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Blood and Lymphatic System Disorders | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Cellulitis | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Chronic sinusitis | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Hypotension | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Respiratory, Thoracic and Mediastinal Disorders | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Wound infection | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Colon cancer | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | General Disorders and Administration Site Conditions | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Haematoma | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Rhonchi | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Injection site bruising | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Peripheral arterial occlusive disease | 2 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Pyrexia | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Metastases to liver | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Vascular Disorders | 2 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Pain in extremity | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Investigations | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Blood creatinine increased | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Blood glucose increased | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Ileus | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Glucose urine present | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Muscle spasms | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | International normalized ratio increased | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Gastric ulcer | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Prostatic specific antigen increased | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Wheezing | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Skin and Subcutaneous Tissue Disorders | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Gastrointestinal Disorders | 1 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Chest pain | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Erythema | 0 Participants |
| Cohort 3 | Treatment-Emergent Adverse Events. | Musculoskeletal pain | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | General Disorders and Administration Site Conditions | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Blood glucose increased | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Musculoskeletal pain | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Colon cancer | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Skin ulcer | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Bundle branch block left | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Throat irritation | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Peripheral arterial occlusive disease | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Injury, Poisoning and Procedural Complications | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Prostatic specific antigen increased | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Respiratory, Thoracic and Mediastinal Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Injection site bruising | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Tongue injury | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Cardiac Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Gastrointestinal Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Cellulitis | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Psychiatric Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Glucose urine present | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Pyrexia | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Confusional state | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Chest pain | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps) | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Vascular Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Subjects with at least one TEAE | 3 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Anaemia | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Gastric ulcer | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Cyanosis | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Infections and Infestations | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Small cell lung cancer stage unspecified | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Pruritus | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Urinary tract infection | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Blood and Lymphatic System Disorders | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Metastases to liver | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | International normalized ratio increased | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Upper respiratory infection | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Investigations | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Biliary adenoma | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Skin and Subcutaneous Tissue Disorders | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Hypotension | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Rhonchi | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Pain in extremity | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Chronic sinusitis | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Muscle spasms | 1 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Blood creatinine increased | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Ileus | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Wound infection | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Haematoma | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Wheezing | 0 Participants |
| Cohort 4 | Treatment-Emergent Adverse Events. | Erythema | 0 Participants |
Secondary
Change From Baseline in Ankle Brachial Index
The Ankle Brachial Index is the ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the upper arm (brachial). Outcome measure is the Change in Baseline from Day 0 (Baseline) to Actual visit Days (Days 15, 28, 59, 91, 180 and 365).
Time frame: Days 15, 28, 59, 91, 180, and 365
Population: Intent-to-treat population, defined as all subjects who received at least one dose of study drug and had at least one post-dose assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Baseline (Day 0) Actual values only | 0.35 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.1 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 180 | 0.06 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.14 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 91 | 0.14 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.09 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 15 | 0.10 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.12 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 365 | 0.12 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.06 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 28 | 0.0 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.14 |
| Cohort 1 | Change From Baseline in Ankle Brachial Index | Day 59 | 0.08 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.08 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 180 | 0.07 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.11 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 59 | 0.14 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.14 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 28 | 0.14 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.07 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 91 | 0.05 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.13 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 365 | 0.21 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.15 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Day 15 | 0.05 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.04 |
| Cohort 2 | Change From Baseline in Ankle Brachial Index | Baseline (Day 0) Actual values only | 0.35 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.04 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 59 | -0.10 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.17 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Baseline (Day 0) Actual values only | 0.44 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.06 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 15 | 0.02 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.02 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 28 | -0.06 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.17 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 91 | -0.03 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.03 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 180 | -0.05 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.08 |
| Cohort 3 | Change From Baseline in Ankle Brachial Index | Day 365 | 0.13 Ratio Systolic BP-Change ankle to arm | — |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 28 | -0.08 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.38 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 365 | 0.13 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.19 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 180 | 0.15 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.05 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 15 | 0.04 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.14 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Baseline (Day 0) Actual values only | 0.57 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.43 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 91 | 0.09 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.32 |
| Cohort 4 | Change From Baseline in Ankle Brachial Index | Day 59 | 0.13 Ratio Systolic BP-Change ankle to arm | Standard Deviation 0.24 |
Secondary
Change From Baseline in Pain Visual Analog Scale
Pain intensity was assessed by subjects marking a place on a 100 mm Visual Analog Scale ranging from 0 = no pain to 100 = worst possible pain. The distance from 0 to the mark was to be measured in millimeters (0 to 100 mm).
Time frame: Days 15, 28, 59, 91, 180, and 365
Population: The Intent-to-Treat population included all subjects who received at least one dose of study drug medication and had at least one post-dose assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Baseline (Day 0) Actual values only | 66.7 score on a scale | Standard Deviation 20.79 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 180 | -12.3 score on a scale | Standard Deviation 22.68 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 91 | -3.3 score on a scale | Standard Deviation 29.02 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 15 | -0.3 score on a scale | Standard Deviation 19.3 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 365 | -13.7 score on a scale | Standard Deviation 35.5 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 28 | 4.0 score on a scale | Standard Deviation 14.42 |
| Cohort 1 | Change From Baseline in Pain Visual Analog Scale | Day 59 | -8.3 score on a scale | Standard Deviation 30.01 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 180 | -63.3 score on a scale | Standard Deviation 12.22 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 59 | -52.0 score on a scale | Standard Deviation 10.39 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 28 | -53.7 score on a scale | Standard Deviation 18.88 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 91 | -56.3 score on a scale | Standard Deviation 9.07 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 365 | -63.3 score on a scale | Standard Deviation 13.61 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Day 15 | -20.7 score on a scale | Standard Deviation 22.19 |
| Cohort 2 | Change From Baseline in Pain Visual Analog Scale | Baseline (Day 0) Actual values only | 64.3 score on a scale | Standard Deviation 12.9 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 59 | 13.0 score on a scale | Standard Deviation 9 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Baseline (Day 0) Actual values only | 38.3 score on a scale | Standard Deviation 45.79 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 15 | 1.7 score on a scale | Standard Deviation 9.87 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 28 | 8.7 score on a scale | Standard Deviation 7.23 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 91 | 1.0 score on a scale | Standard Deviation 11.36 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 180 | 31.0 score on a scale | Standard Deviation 55.15 |
| Cohort 3 | Change From Baseline in Pain Visual Analog Scale | Day 365 | 37.5 score on a scale | Standard Deviation 58.69 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 28 | -15.3 score on a scale | Standard Deviation 3.06 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 365 | 4.3 score on a scale | Standard Deviation 9.87 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 180 | -29.7 score on a scale | Standard Deviation 19.55 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 15 | 7.0 score on a scale | Standard Deviation 19.67 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Baseline (Day 0) Actual values only | 50.3 score on a scale | Standard Deviation 20.31 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 91 | 0.0 score on a scale | Standard Deviation 38.11 |
| Cohort 4 | Change From Baseline in Pain Visual Analog Scale | Day 59 | -26.3 score on a scale | Standard Deviation 14.57 |
Secondary
Change From Baseline in Toe Brachial Index
Toe brachial index is the ratio of the systolic blood pressure of the toes to the systolic blood pressure in the upper arm (brachial). Outcome measure is the Change in Ratio for Baseline from Day 0 (Baseline) to Actual visit Days (Days 15, 28, 59, 91, 180 and 365).
Time frame: Baseline and Days 1,15,28,59,91,180,and 365
Population: Intent-to-treat population defined as all subjects who received at least one dose of study drug and had at least one post-dose assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline in Toe Brachial Index | Baseline (Day 0) Actual values only | 0.16 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.04 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 180 | 0.05 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.06 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 91 | 0.04 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.15 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 15 | 0.0 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.07 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 365 | 0.10 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.07 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 28 | -0.01 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.09 |
| Cohort 1 | Change From Baseline in Toe Brachial Index | Day 59 | 0.08 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.09 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 180 | 0.10 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.12 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 59 | 0.05 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.05 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 28 | -0.01 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.02 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 91 | 0.06 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.04 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 365 | 0.14 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.11 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Day 15 | 0.07 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.05 |
| Cohort 2 | Change From Baseline in Toe Brachial Index | Baseline (Day 0) Actual values only | 0.19 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.01 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 59 | -0.04 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.09 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Baseline (Day 0) Actual values only | 0.18 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.11 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 15 | -0.05 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.13 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 28 | -0.02 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.08 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 91 | -0.08 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.08 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 180 | 0.01 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.12 |
| Cohort 3 | Change From Baseline in Toe Brachial Index | Day 365 | -0.08 Ratio Systolic BP-Change toe to arm | — |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 28 | 0.03 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.01 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 365 | 0.11 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.03 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 180 | 0.01 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.22 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 15 | 0.22 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.01 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Baseline (Day 0) Actual values only | 0.22 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.26 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 91 | 0.12 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.06 |
| Cohort 4 | Change From Baseline in Toe Brachial Index | Day 59 | 0.14 Ratio Systolic BP-Change toe to arm | Standard Deviation 0.03 |
Secondary
Change From Baseline in Transcutaneous Oxygen Pressure
At Screening, transcutaneous oxygen pressure was measured at pre-defined locations on the anterior and posterior calf and dorsum of the foot. The limb/chest Transcutaneous Oxygen Pressure index was calculated by using the lower of the distal limb measurements
Time frame: Days 1 to 365
Population: Intent-to-treat population defined as all subjects who received at least one dose of study drug and had at least one post-dose assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline in Transcutaneous Oxygen Pressure | Baseline (Day 0) Actual values only | 48.7 mmHg | Standard Deviation 12.1 |
| Cohort 1 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 91 | 10.0 mmHg | Standard Deviation 8.72 |
| Cohort 1 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 180 | 15.0 mmHg | Standard Deviation 10.54 |
| Cohort 1 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 365 | 9.0 mmHg | Standard Deviation 7.81 |
| Cohort 2 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 91 | 4.3 mmHg | Standard Deviation 13.87 |
| Cohort 2 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 180 | 13.0 mmHg | Standard Deviation 6.24 |
| Cohort 2 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 365 | 7.3 mmHg | Standard Deviation 7.64 |
| Cohort 2 | Change From Baseline in Transcutaneous Oxygen Pressure | Baseline (Day 0) Actual values only | 47.0 mmHg | Standard Deviation 18.03 |
| Cohort 3 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 180 | 10.0 mmHg | Standard Deviation 11.31 |
| Cohort 3 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 91 | 2.7 mmHg | Standard Deviation 13.32 |
| Cohort 3 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 365 | 25.5 mmHg | Standard Deviation 2.12 |
| Cohort 3 | Change From Baseline in Transcutaneous Oxygen Pressure | Baseline (Day 0) Actual values only | 38.3 mmHg | Standard Deviation 11.02 |
| Cohort 4 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 365 | -3.7 mmHg | Standard Deviation 7.37 |
| Cohort 4 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 91 | -1.3 mmHg | Standard Deviation 5.13 |
| Cohort 4 | Change From Baseline in Transcutaneous Oxygen Pressure | Baseline (Day 0) Actual values only | 70.7 mmHg | Standard Deviation 4.51 |
| Cohort 4 | Change From Baseline in Transcutaneous Oxygen Pressure | Day 180 | -16.3 mmHg | Standard Deviation 21.96 |