A Phase 2a Multicenter, Randomized, Double-blind, Placebo-controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, of HBI-002, an Oral Low-dose Carbon Monoxide (CO) Liquid Drug Product, Administered Daily Over 14 Days in Subjects With Parkinson's Disease (PD)
A phase 2a multicenter, randomized, double-blind, placebo-controlled multiple dose study to evaluate the safety, tolerability, pharmacokinetics, of HBI-002, an oral low-dose carbon monoxide (CO) liquid drug product, administered daily over 14 days in subjects with Parkinson's disease (PD).
• Subjects must meet the following criteria before being enrolled into the study:
• Signed informed consent.
• Male or female 40-80 years of age
• Non-smoker for at least 5 years with smoking defined as the use of smoked products (e.g. tobacco, marijuana, vaping or other)
• No smoking in the home (i.e. not living with a smoker)
• Body weight between 60 kg and 110 kg (inclusive) and with BMI less than 30 kg/m2 at screening and baseline
• Diagnosis of PD according to the Movement Disorder Society within 60 months of screening
• Hoehn and Yahr stage ≤ 3
• PD therapy: use of ≥100 mg TID levodopa or equivalent dose with additional carbidopa/levodopa or other antiparkinsonian medication (e.g. dopamine agonists \[e.g., pramipexole, ropinirole, rotigotine\] and monoamine oxidase inhibitors \[e.g., selegiline or rasagiline\]) for ≥30 days of stable dosing
• Good clinical response to levodopa therapy in the Site Investigator's opinion
⁃ Negative pregnancy test for females of childbearing potential
⁃ Where appropriate, subjects must be willing to use a highly effective method of contraception for the duration of the study and for 45 days thereafter
∙ Male subjects, without a vasectomy, whose partner is of childbearing potential, must use a condom and be instructed that their female partner should use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant or a tubal ligation. Male subjects are prohibited from donating sperm for the duration of the study and 60 days following the end of study visit.
‣ Female subjects of childbearing potential (not surgically sterilized and less than one year post-menopausal) should use a medically accepted form of contraception such as an IUD, diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant or a tubal ligation, and be instructed that their male partners should use a condom, if not vasectomized.
⁃ Subjects must be healthy as defined by the following.
∙ liver function: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2X ULN
‣ total bilirubin ≤ 1.5X ULN
‣ renal function: creatinine clearance within normal range as assessed by Cockcroft and Gault calculation
‣ carboxyhemoglobin level by venous blood gas ≤ 3.5%
‣ the absence of current clinically relevant abnormalities identified by a detailed medical history, full physical examination including blood pressure, pulse rate, and respiratory rate measurement, 12-lead ECG, and clinical laboratory tests (hematology and clinical chemistries), as determined by the Site Investigator.
‣ HbA1c \< 6.5%
⁃ Subjects must have a study partner who can observe the subject for at least 4 hours after dosing at home (non-clinic days) in order to monitor for indications of CO toxicity.
⁃ Subjects should live within 100 miles driving distance (door to door) of the site/clinic due to the need to carry study drug and ship study drug between the site/clinic and subject's home. Exceptions to this may be considered with Sponsor approval if it can be assured that the subject can transport study drug from clinic to home within two hours.