a first in human, dose escalation study to evaluate the safety and tolerability of bbp-671 in healthy volunteers and patients with propionic acidemia or methylmalonic acidemia

Conditions: Healthy Volunteers; Propionic Acidemia; Methylmalonic Acidemia; Organic Acidemia

Summary: the purpose of this study is to assess the safety, tolerability, pk and pd of bbp-671 in healthy volunteers and patients with propionic acidemia or methylmalonic acidemia.

this is the first-in-human study with bbp-671 and is designed to provide healthy subjects single- and multiple-dose and patient multidose safety, tolerability, pk, and pd data regarding bbp-671 for future clinical studies.

Eligibility criteria:
inclusion criteria (healthy volunteers): * subject is male or female 18 to 55 yrs old * subject has a bmi 18 to 32 kg/m\^2 * female and male subjects must use effective method of birth control * female subjects must have negative pregnancy test prior to first dose of study drug * subject must not have any clinically significant history or presence of ecg findings * subject must be in good general health inclusion criteria (pa or mma patients): * patient is male or female 15 to 55 yrs old * patient has a bmi 18 to 32 kg/m\^2 * female and male patients must use effective method of birth control * female patients must have negative pregnancy test prior to first dose of study drug * patient must have confirmed pa or mma diagnosis * patient with mma must have elevated plasma mma levels * patient is willing to provide access to medical records for the last 6-12 months of care prior to study initiation * patient is on consistent disease management and treatment regimen is stable for at least 30 days prior to study initiation. exclusion criteria (healthy volunteers): * subject has used prescription drugs (contraceptive medications are allowed) within 4 weeks before first dose of study drug or over-the-counter medication within 7 days of the first dose of study drug * subject who is unable or unwilling to refrain from wearing contact lenses during participation in the study. * subject has a history of dry eye or eye surgery, including radial keratotomy and lasik surgery. * subject who has taken the covid-19 vaccine, the last vaccine dose must be at least 14 days prior to first dose of study drug. * subject has abnormal laboratory test results * subject has a baseline egfr \<90 ml/minute * subject has positive result for hepatitis b, hepatitis c, or hiv * female subject is non-pregnant and non-lactating * subject is a smoker or has used nicotine or nicotine-containing products * subject has a history of alcohol or drug abuse within 12 months prior to first dose of study drug and/or has a positive result prior to dosing or throughout the study * subject has donated blood or blood products \>450ml within 30 days prior to study drug dosing * subject has a history of relevant drug or food allergies * subject has received study drug in another investigational study within 30 days of dosing * subject has undergone prior liver and/ or kidney transplant. exclusion criteria (pa or mma patients): * patient has used prescription drugs (contraceptive medications are allowed) within 4 weeks before first dose of study drug or over-the-counter medication within 7 days of the first dose of study drug that is not part of their pa or mma disease management and treatment * patient who has taken the covid-19 vaccine, the last vaccine dose (or booster) must be at least 14 days prior to first dose of study drug. * patient is unable or unwilling to refrain from wearing contact lenses during participation in the study. * patient has a history of dry eye or eye surgery, including radial keratotomy and lasik surgery. * patient has clinically significant abnormal laboratory test results unrelated to pa or mma * patient has a baseline egfr \<60 ml/minute * patient has positive result for hepatitis b, hepatitis c, or hiv * female patient is non-pregnant and non-lactating * patient has a history of alcohol or drug abuse within 12 months prior to first dose of study drug and/or has a positive result prior to dosing or throughout the study * patient has donated blood or blood products \>450ml within 30 days prior to study drug dosing * patient has a history of relevant drug or food allergies * patient has received study drug in another investigational study within 30 days of dosing * pa patient has undergone prior liver and/ or kidney transplant. prior liver and/or kidney transplant is allowed for patients with mma. * patient has had a recent infection requiring system antibiotics within 4 weeks of baseline or any active infection that precludes the patient from participation * patient has grade 3 or 4 heart failure according to the modified ross heart failure classification for children or the new york heart association. * patient has been exposed to gene therapy for pa or mma at any time prior to study entry. * patient is currently taking sensitive cyp3a4 substrates (e.g., tacrolimus or sirolimus)