Food Effect in Healthy Participants
Conditions
Brief summary
This study will explore the potential effects of high-fat meal on the plasma pharmacokinetics (PK) of CRS3123 when administered as a single oral dose of 200 mg in healthy adult participants.
Detailed description
This study will assess the impact of a high-calorie and high-fat meal on the plasma pharmacokinetics (PK) of CRS3123 in healthy adult participants when administered as a single oral capsule of 200 mg dose. Pharmacokinetics (PK) of a single dose of CRS3123 200 mg will be studied following administration to healthy participants under fed and fasted conditions.
Interventions
DRUGCRS3123 200 mg capsule
CRS3123 200 mg capsule given as a single oral dose
Sponsors
Crestone, Inc
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
In each period, participants will receive Treatment A or Treatment B according to the randomization scheme: * Treatment A: No food will be allowed from at least 10 hours before dosing until at least 4 hours after dosing. * Treatment B: After a supervised overnight fast of at least 10 hours, participants will be served a high-calorie and high-fat breakfast, in compliance with the FDA Guidance for Industry: Assessing the Effects of Food on Drugs in INDs and NDAs - Clinical Pharmacology Considerations (2022). Breakfast will be served approximately 30 minutes prior to CRS3123 administration. Participants will fast for no less than 4 hours after study drug administration.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Non-pregnant and non-lactating adults, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), ≥ 18 and ≤ 64 years of age, with body mass index (BMI) \> 18.5 and \< 30.0 kg/m2 and body weight ≥ 50.0 kg for males (as assigned at birth) and ≥ 45.0 kg for females (as assigned at birth), at the time of signing the informed consent. 2. Healthy as defined by: 1. the absence of clinically significant physical or laboratory findings (above Grade 1) and surgery within 4 weeks prior to dosing. 2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal (GI), renal, hepatic, and metabolic disease. 3. Healthy females (as assigned at birth) of non-childbearing potential must be: 1. postmenopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented follicle stimulating hormone (FSH) levels greater than or equal to 40 mIU/mL; or 2. surgically sterile (bilateral oophorectomy, hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, bilateral salpingectomy, hysterectomy or tubal ligation) at least 3 months prior to dosing. 4. Sexually active females (as assigned at birth) of childbearing potential and non-sterile males (as assigned at birth) must be willing to use an acceptable contraceptive method throughout the study. 5. Able to understand the study procedures and provide signed informed consent to participate in the study.
Exclusion criteria
1. Any clinically significant abnormal finding at physical examination at screening that may interfere with the interpretation of safety and PK objectives of the study. 2. Abnormal laboratory test results (above Grade 1) that may interfere with the interpretation of safety and PK objectives of the study. 3. Positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antigen and antibody. 4. History of current or chronic liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 5. Positive pregnancy test at screening or admission to the clinical research unit. 6. Positive urine drug screen, urine cotinine test, or alcohol test at screening or admission to the clinical research unit. 7. Known allergic reactions to CRS3123 or other related drugs, or to any excipient in the formulation. 8. Use of medications within specified timeframes. 9. Previous exposure to CRS3123 within 12 months prior to the first dose. 10. Participants with HR \< 50 or \> 100 beats per minute (bpm), systolic blood pressure (SBP) \< 90 or \> 140 mmHg, diastolic blood pressure (DBP) \< 50 or \> 90 mmHg, on vital sign assessment at screening or admission to the clinical research unit. 11. A baseline ECG at screening with corrected QT interval (QTc) using Fridericia's formula (QTcF) \> 450 msec. 12. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any clinically significant (above Grade 1) conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block \[second degree or higher\], Wolf Parkinson White syndrome), sinus pauses \> 3 seconds, non sustained or sustained ventricular tachycardia (≥ 3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the Investigator will interfere with the safety of the individual participant. 13. Participant has any surgical or medical condition (active or chronic) or GI tract condition (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, irritable bowel syndrome, inflammatory bowel disease, or any other condition that may interfere with normal gastric emptying or transit time) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the participant at risk, in the opinion of the Investigator. 14. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days or 5× t½ (whichever is longer) prior to the first dose, administration of a biological product in the context of a clinical research study within 90 days or 5× t½ (whichever is longer) prior to the first dose or concomitant participation in an investigational study involving no drug or device administration. 15. Participants with serum creatinine level \> 1.5 mg/dL. 16. History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening. 17. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%). 18. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to first dosing. 19. Participant is unable to comply with all the study procedures in the opinion of the Investigator. 20. Any reason the participant should not participate in the study in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Food Effect Based on CRS3123 PK Parameters AUC0-t, AUC0-inf, and Cmax | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | CRS3123 PK parameters (AUC0-t, AUC0-inf, Cmax) values plotted against food status. Note: no food-effect is assumed if the 90% CI for the ratio of geometric means (B (fed)/A (fasted), based on least-squares means from the ANOVA of the ln-transformed CRS3123 AUC0-inf (or AUC0-t) AND Cmax, is within 80.00% to 125.00% for CRS3123. |
| Calculation of AUC0-t for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Area under the concentration-time curve from time zero until the last observed concentration under fasted vs fed conditions |
| Calculation of AUC0-inf for CRS3123 Under Fasted vs Fed Conditions. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Area under the concentration-time curve from time zero to infinity (extrapolated) under fasted vs fed conditions. |
| Calculation of Cmax for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Maximal observed concentration under fasted vs fed conditions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calculation of Tmax for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Time when the maximal concentration is observed under fasted vs fed conditions |
| Calculation of Tlag for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Time of observation prior to the first observation with a measurable (non-zero) concentration under fasted vs fed conditions |
| Calculation of t1/2 for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Terminal elimination half-life under fasted vs fed conditions |
| Calculation of Kel for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Terminal elimination rate constant under fasted vs fed conditions |
| Calculation of Cl/F for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Apparent clearance under fasted vs fed conditions |
| Calculation of Vz/F for CRS3123 Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Apparent volume of distribution under fasted vs fed conditions |
| Calculation of Tmax for CRS3123-glu3 Metabolite Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Time when the maximal concentration is observed under fasted vs fed conditions |
| Calculation of Tlag for CRS3123-glu3 Metabolite Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Time of observation prior to the first observation with a measurable (non-zero) concentration under fasted vs fed conditions |
| Calculation of t1/2 for CRS3123-glu3 Metabolite Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Terminal elimination half-life under fasted vs fed conditions |
| Calculation of Kel for CRS3123-glu3 Metabolite Under Fasted vs Fed Conditions | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours post-dose on Day 1 and Day 6 | Terminal elimination rate constant under fasted vs fed conditions |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41 Years |
| BMI | 25.5 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 162 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 69.2 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 5 / 17 | 6 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
None listed