Healthy Volunteer, Pharmacokinetics After Oral Intake
Conditions
Keywords
Pharmacokinetics, Relative Bioavailability, Crossover, ARN-75039, HPMC capsule, Tablet With Excipients
Brief summary
ARN-75039-103 is a comparative, randomized, single-dose, cross-over study to assess the PK, safety, and tolerability of neat ARN-75039 in hydroxypropyl methylcellulose (HPMC) capsules compared with ARN-75039 with excipients in tablet form, both administered orally, in healthy adult participants. The safety assessments will include standard evaluations of vital signs, clinical laboratory values, and ECGs. Participants will be admitted to the study site on the morning of Day -1, before Period 1 study drug administration, and will remain on site until Day 15. Upon confirmation of eligibility, participants will be randomized into the study on Day 1. Study drug administration will be performed on the first day of Periods 1 and 2 (Study Days 1 and 8, respectively) with a 7-day washout period between the two periods. Participants will receive the randomized study drug in the morning following a meal. A total of 16 participants will be randomized 1:1 to the following two sequences: * Sequence 1: * Form A: Neat ARN-75039 in HPMC capsules (reference product) * Form B: ARN-75039 with excipients in tablet form (comparator) * Sequence 2: * Form B: ARN-75039 with excipients in tablet form (comparator) * Form A: Neat ARN-75039 in HPMC capsules (reference product) Participation in the study will be conducted in the following 5 defined periods: * Screening Period: The Screening Period begins upon completion of the informed consent form (ICF). During this period, participants will undergo baseline assessments to determine eligibility for study participation. The Screening Period duration will be up to 21 days; it will end after all evaluations required to meet eligibility have been completed. If a participant meets all eligibility criteria, they will be offered enrollment into the study. * Admission to Study Site: Participants will be admitted to the study site in the morning on the day before dosing of period 1 (Day -1). Participants who are eligible to participate in the study and are randomized into the study will remain at the study site until completion of the treatment period (Study Day 15). * Treatment Period: This study consists of two treatment days separated by a 7-day washout period. The first treatment day will begin on Day 1 of Period 1 with administration of the first dose of study drug. The second treatment day will occur on the first day of Period 2 (Study Day 8). Following the dosing of the study drug on each treatment day, fifteen venous blood samples will be withdrawn via an indwelling cannula or by venipuncture at regular time intervals. * End of Active Treatment (Day 15 Discharge Visit or Early Termination (ET) Visit): Upon successful completion of active treatment, participants will be discharged from the study site on Study Day 15. The Discharge Visit will include the completion of safety assessments, such as a physical examination, vitals, ECG recording, adverse event review, and clinical laboratory tests. Participants who complete both dosing days will be encouraged to complete all study visits. Participants who do not complete all study visits or terminate from the study before Day 15 will be asked to complete The Early Termination Visit is within 1 day after withdrawal from the study. • Day 36 Telephone Follow-Up Phone Call: Participants will be contacted by phone on Day 36-i.e., 28 days following the last study dose administered on Day 8. The purpose of this follow-up call is to assess for any adverse events.
Detailed description
Two-period cross-over, Form A vs Form B, fed, inpatient Day -1 through Day 15, Day 36 follow-up
Interventions
DRUGARN-75039
An oral therapy for the treatment of Lassa infection
Sponsors
Arisan Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This study used a 2-period, 2-sequence crossover design (Sequence 1: A→B; Sequence 2: B→A). All 16 randomized participants completed both periods and contributed data to both formulations. Participant numbers per arm in the results represent treatment at the time of measurement, not unique participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Participants meeting all the following criteria are eligible for study participation: 1. Is male or female, age 18 to 45 years, inclusive, at Screening. 2. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at Screening. 3. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Day -1 or 1. 4. Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the laboratory reference range at Screening or without clinically significant abnormalities in the opinion of the Investigator; participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities. 5. Estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥ 80 mL/min/1.73 m2 at Screening. 6. Females of childbearing potential must practice effective contraception per national regulatory guidelines for clinical trials from Screening (see Section 5.6.2), throughout the study, and for 60 days after the last dose of study drug. 7. Females must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal participants, a blood sample will also be tested for estradiol and follicle stimulating hormone (FSH) to confirm post-menopausal status based on reference laboratory ranges for post-menopausal status. Surgically sterile females are eligible; however, proof via medical records will be required. 8. Males must agree to not donate sperm and to use condom and spermicide in combination with any of the means of contraception for their female partners during sexual intercourse from the time of the first study drug administration and for 90 days following the last dose of study drug. Females must agree not to donate eggs from the time of the first study drug administration and for 60 days following the last dose of study drug. 9. Must be willing and able to comply with measures to avoid photosensitivity reactions (i.e., avoidance of outdoor sun exposure and tanning; consistent use of long sleeve shirts, long pants, hats, and sunglasses; consistent use of sun protection factor \[SPF\] 75 or greater sunscreen when outdoors) during the study treatment period. 10. Able to consume a standard meal (400-600 Calories) within 30 minutes. 11. Able to provide informed consent. 12. Willing and able to comply with this protocol and be available for the entire duration of the study.
Exclusion criteria
Participants meeting any of the following criteria are not eligible for study participation: 1. Any clinically significant underlying illness in the opinion of the Investigator. 2. Poor venous access. 3. Prior exposure to ARN-75039. 4. History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Day -1. 5. Use of any prescription or over-the-counter (OTC) medications, including food supplements, vitamins, herbal medications (e.g., St. John's wort), and cannabis, with the exception of contraceptive medications and as needed (prn) acetaminophen or paracetamol (not exceeding 2 grams/day) within 7 days prior to study drug administration and through the Day 15 Discharge visit. 6. Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and safety follow-up period. 7. Currently enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives of the prior investigational agent (whichever is longer) or plans to enroll in another investigational device or drug study during the course of this study. 8. Inability to ingest all capsules/tablets of a multi-capsule dose within 5 minutes of ingestion of the first capsule/tablet. 9. Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at Screening; participants with adequately treated HCV are eligible for enrollment. 10. Consumption of Seville oranges, grapefruit or grapefruit juice within 72 hours prior to Day 1 or during the study. 11. History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix. 12. Smoking cigarettes, cigars, cigarillos or E-cigarettes 13. Any reason or condition that, in the investigator's opinion, may compromise study participation, present a safety risk to the participant, or may confound the interpretation of the study results. 14. A QT duration corrected for heart rate by Fridericia's formula (QTcF) \> 450 millisecond (msec) based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval (at Screening). 15. Blood product (including plasma) donation within 30 days before Screening. 16. Unwilling to consume a breakfast on study drug administration days. 17. History of: * Structural abnormality of the GI tract or a disease or history of a condition that can affect GI motility. * Inflammatory bowel disease (even if treated and currently in remission). * Diverticulitis or any other chronic condition such as chronic pancreatitis, polycystic kidney disease, ovarian cysts, endometriosis, lactose intolerance that can be associated with abdominal pain or discomfort and could confound the assessments in this trial. * Chronic idiopathic diarrhea. 18. Formally diagnosed colonic inertia or conditions that can be associated with constipation: pseudo-obstruction, colonic inertia, megacolon, megarectum, bowel obstruction, descending perineum syndrome, solitary rectal ulcer syndrome, systemic sclerosis, lower tract evacuation disorders, functional outlet delay (e.g., rectal prolapse, anismus, etc.). 19. Current active peptic ulcer disease (i.e., disease that is not adequately treated or stable with therapy.) 20. Potential central nervous system cause of constipation (e.g., Parkinson's disease, spinal cord injury, and multiple sclerosis). 21. Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding \[rectal bleeding or heme-positive stool\], iron-deficiency anemia or any unexplained anemia, or weight loss) or systemic signs of infection or colitis. 22. History of chronic/generalized pruritus and/or skin rash of unknown origins. 23. Participants with diagnosed Type 1 or Type 2 diabetes, or with a fasting blood glucose value \> 125 mg/dL during the screening period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t | From time zero (dose) to time of last quantifiable concentration. Period 1: 0 to 144 hours; Period 2: 0 to 168 hours. | Area Under the Plasma-drug Concentration Time Curve from time zero to time of last quantifiable concentration. Compare the pharmacokinetic (PK) properties of 300mg ARN-75039 with excipients in tablet form to 300mg neat ARN-75039 in HPMC capsules following oral administration under fed conditions. |
| AUC0-24 | From time zero (dose) to 24 hours post-dose. | Area under the plasma concentration-time curve from time zero to 24 hours post-dose. Compare the pharmacokinetic (PK) properties of 300mg ARN-75039 with excipients in tablet form to 300mg neat ARN-75039 in HPMC capsules following oral administration under fed conditions. |
| AUC0-∞ | From time zero (dose) extrapolated to infinity. Time frame is from 0 to Tlast + extrapolation from C last to infinity time, where concentration is equal to 0. | Area under plasma concentration-time curve from time zero to infinity. Compare the pharmacokinetic (PK) properties of 300mg ARN-75039 with excipients in tablet form to 300mg neat ARN-75039 in HPMC capsules following oral administration under fed conditions. |
| Cmax | From time 0 (dose) through 168 hours post-dose. | Maximum observed plasma concentration. Compare the pharmacokinetic (PK) properties of 300mg ARN-75039 with excipients in tablet form to 300mg neat ARN-75039 in HPMC capsules following oral administration under fed conditions. |
| Tmax | From time 0 (dose) through 168 hours post-dose. | Time to reach Cmax |
| t1/2 | From time 0 (dose) through 168 hours post-dose (terminal elimination phase). | Half-life |
| CL/F | From time 0 (dose) through 168 hours post-dose (derived from the concentration-time profile). | Apparent clearance after extravascular administration. |
| Vz/F | From time 0 (dose) through 168 hours post-dose (derived from the concentration-time profile). | Apparent volume of distribution during the terminal phase after extravascular administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With ≥1 TEAE | From first dose through approximately 7 days after the last dose (includes washout); with Day 36 follow-up phone call to assess for any adverse events (AEs). | Type and frequency of treatment-emergent adverse events (TEAEs). |
| Participants With ≥1 TESAE | From first dose through approximately 7 days after the last dose (includes washout); with Day 36 follow-up phone call to assess for any adverse events (AEs). | Type and frequency of treatment-emergent serious adverse events (TESAEs). |
| Participants With Study Drug-related TEAEs of Grade >1 | From first dose through approximately 7 days after the last dose (includes washout); with Day 36 follow-up phone call to assess for any adverse events (AEs). | Type and frequency of study drug-related \>Grade 1 TEAEs |
Countries
United States
Contacts
STUDY_CHAIRKen McCormack, PhD
Arisan Therapeutics
Participant flow
Recruitment details
Sixteen participants were enrolled, and none discontinued the study early or were excluded from analysis. All the informed consent forms (ICFs) were signed within the window from February 27, 2025 and March 11, 2025.
Pre-assignment details
Two-period, two-sequence crossover (Sequence 1: A→B; Sequence 2: B→A). All 16 randomized participants completed both periods and contributed data to both formulations. Participant numbers shown per arm in the results represent treatment at the time of measurement (not unique participants).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 5.96 |
| Body Mass Index (BMI) | 26.4 kg/m^2 STANDARD_DEVIATION 3.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 167.8 cm STANDARD_DEVIATION 7.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 9 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
| Weight | 74.1 kg STANDARD_DEVIATION 9.96 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
None listed