Evaluation of Safety, Tolerability and Preliminary Efficacy of Etrinabdione in Patients With Peripheral Arterial Disease

This is a single center, open-label Phase IIa clinical study. The study will be conducted with 2 treatment arms 25 mg BID and 50 mg BID.

The study consists of a Screening Period, a Treatment Period, and a Follow-up Period. Total duration 14 months.

Subjects who meet the inclusion criteria and do not meet the exclusion criteria at screening will start with the lower dose (25 mg BID). When the 12 patients have been treated for 3 months and the PK and safety data are evaluated by the regulatory authority, the Sponsor and the site investigators, the high dose (50 mg BID) will be released.

Inclusion criteria

• Willing and able to provide informed consent and capable of understanding and complying with the protocol;
• Subjects classified as critical limb ischemia (CLI) Rutherford Category 2 or 3 (moderate or severe) claudication;
• Diabetes mellitus type 2 with HbA1c < 9%;
• In case of treatment for PAD, the subject is controlled on medical therapy indicated for CLI;
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use a highly effective method of contraception;
• A male patient with a female partner of childbearing potential is eligible if he agrees to use acceptable method of contraception.

Exclusion criteria

• Planned surgical or endovascular revascularization on the index leg within the next 12 months;
• Failed surgical or endovascular revascularization on the index leg within 10 days prior to screening;
• Amputation at or above the talus on the index leg;
• Planned major amputation within the first month after screening;
• On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new treatments to the index leg during the trial;
• Uncontrolled or untreated proliferative retinopathy;
• Blood clotting disorder not caused by medication;
• Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure;
• Evidence of moderate to severe hepatocellular dysfunction;
• Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema Pallidum;
• Subjects who may not be healthy enough to successfully complete all protocol requirements, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess.