Healthy Volunteers, Methylmalonic Acidemia, Organic Acidemia, Propionic Acidemia
Conditions
Brief 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.
Detailed description
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.
Interventions
DRUGBBP-671
BBP-671, oral suspension
DRUGPlacebo
Placebo matching BBP-671
Sponsors
CoA Therapeutics, Inc., a BridgeBio company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Assessments: CLr | 15 days | Renal clearance (CLr) |
| Pharmacokinetic Assessments: t1/2 | 49 days | Plasma decay half-life (t1/2) |
| Pharmacokinetic Assessments: AUC0-tau | 49 days | Area under the plasma concentration-time curve (AUC0-tau) |
| Pharmacokinetic Assessments: CL/F | 15 days | Apparent clearance (CL/F) |
| Pharmacokinetic Assessments: Vz/F | 15 days | Apparent volume of distribution (Vz/F) |
| Incidence of adverse events following administration of BBP-671 | 49 days | — |
| BBP-671 concentration dependent change in change from baseline in QTcF | 49 days | — |
| Pharmacokinetic Assessments: Cmax | 49 days | Time to maximum concentration (Cmax) |
| Pharmacokinetic Assessments: Tmax | 49 days | Time to reach maximum observed plasma concentration (Tmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Food Effect: Tmax | 10 days | Time to reach maximum observed plasma concentration |
| Food Effect: AUC | 10 days | Area under the plasma concentration-time curve |
| Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters | 49 days | Measurement will be done using liquid chromatography-tandem mass spectrometry |
| Food Effect: Cmax | 10 days | Time to maximum concentration |
Countries
United States
Outcome results
None listed