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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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ARN-75039 is proposed for the treatment of subjects with LASV infection, Lassa hemorrhagic fever, a potentially fatal human disease associated with Lassa viruses, with the most significant unmet medical need. ARN-75039-101 study was a randomized, double-blind, placebo-controlled study that assessed the safety, tolerability, and PK of escalating single and multiple doses of ARN 75039 when administered by the oral route in healthy adult subjects in six single ascending dose (SAD - Part 1) cohorts and five multiple ascending dose (MAD - Part 2) cohorts.
In Part 1 (SAD), eight subjects per cohort (except for 10 subjects in cohort 3, evaluating the effects of food) were enrolled to receive the study drug orally in the fed state. Within each cohort of eight subjects, the first two subjects (Sentinel) were randomly assigned in a 1:1 ratio to receive a single dose of ARN-75039 capsules or placebo (microcrystalline cellulose). After the medical monitor reviewed the first 3 days of blinded safety for these subjects, an additional 6 subjects (the remaining cohort) were randomly assigned in a 5:1 (active: placebo) ratio. Within the food-effect cohort of 10 subjects, the first two subjects (Sentinel) were randomly assigned in a 1:1 ratio to receive ARN-75039 capsules or a placebo in the fasted state. After the medical monitor reviewed the first three days of blinded safety for these subjects, an additional 8 subjects (the rest of the cohort) were randomly assigned in a 7:1 (active: placebo) ratio.
The Part 2 (MAD) dosing plan consisted of two days of lead-in doses followed by eight days of maintenance dosing. All doses were administered twice daily (BID), approximately 10 hours apart:
The study was conducted in three study periods (Screening Period, Treatment Period, and Follow-up Period). During the Treatment Period, safety was assessed at each study visit, and PK assessments were conducted at specific time points per the assessment schedule. Subjects who received at least one dose of the study drug were instructed and encouraged to complete all study visits. Subjects in the Treatment period had spans of residency at the study site as well as ambulatory periods in each part of the study. Subjects returned to the study site for follow-up evaluations according to the Schedule of Assessments (SOA) during the Treatment Period. After completing the Treatment Period, subjects entered the Safety Follow-up Period, consisting of 14 days for the SAD part of the study and 28 days for the MAD part, culminating in an End-of-study (EOS) visit. For subjects who withdrew from the study prematurely, the EOS visit was conducted within seven days after the last study drug dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARN-75039 oral capsules | Experimental | Escalating single or multiple doses of ARN-75039 oral capsules |
|
| Placebo (microcrystalline cellulose) | Placebo Comparator | Specified weight of placebo (microcrystalline cellulose) corresponding to the dose of ARN-75039 within the same cohort and encapsulating it in a HPMC capsule prior to dosing. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARN-75039 oral capsules | Drug | active oral study drug prepared and administered as oral capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | A treatment-emergent adverse event (TEAE) was defined as any adverse event that began or worsened after administration of the study drug (ARN-75039 or placebo) through the End-of-Study visit. | From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS. |
| Incidence of Treatment-Emergent Serious Adverse Events (TESAEs) | Number of participants with at least one treatment-emergent Serious adverse event (TESAE). A TESAE is any adverse event that starts or worsens after administration of study drug (ARN-75039 or placebo). | From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1-SAD: Cmax | Maximum Observed Plasma Concentrations of ARN-75039 (Cmax); Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. |
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Inclusion Criteria:
Exclusion Criteria:
Any clinically significant underlying illness in the opinion of the Investigator.
Poor venous access.
Inability to ingest all capsules of a multi-capsule dose within 5 minutes of ingestion of the first capsule.
Prior exposure to ARN-75039.
Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at Screening; subjects with adequately treated HCV are eligible for enrollment.
Positive test for SARS-CoV-2 infection on Day -1.
Consumption of Seville oranges, grapefruit or grapefruit juice within 72 hours prior to Day 1 or during the study.
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.
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 EOS visit.
History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix.
Smoking greater than 20 cigarettes, cigars, cigarillos or E-cigarettes per week in the 3 months prior to study drug administration or during the study.
Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and safety follow-up period.
Any reason or condition that, in the investigator's opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
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).
Blood product donation within 30 days before Screening.
unwilling to consume breakfast and dinner on study drug administration days
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.
Part 2 (MAD) only:
History of:
Current active peptic ulcer disease (i.e., disease that was not adequately treated or stable with therapy.)
Potential central nervous system cause of constipation (e.g., Parkinson's disease, spinal cord injury, and multiple sclerosis.)
Subject currently had 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.
Subjects who did not expel at least 80% (19 or more) of the markers after the Sitzmarks® colonic transit test administered during the screening period.
History of chronic/generalized pruritus and/or severe skin rash of unknown origin
Subjects diagnosed with Type 1 or Type 2 diabetes, or with a blood glucose value >125 mg/dL during screening period.
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| Name | Affiliation | Role |
|---|---|---|
| Ken McCormack, PhD | Arisan Therapeutics, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spaulding Clinical, LLC | West Bend | Wisconsin | 53095 | United States |
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This first-in-human, Phase 1, randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics (PK) of oral ARN-75039 in healthy adults, including the effect of food on PK. The study comprised single-ascending-dose (SAD) and multiple-ascending-dose (MAD) parts. Six SAD cohorts (including one food-effect cohort) and five MAD cohorts were conducted. A total of 94 participants were enrolled, and 90 completed the study.
This study was conducted at a single site in the United States from January 23, 2023 (first participant visit) to March 28, 2025 (last participant visit). The study included Screening, Treatment, and Follow-up periods.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1- SAD: Cohort 1 (30mg, Fed) | Participants received a single 30 mg oral dose of ARN-75039 capsules under fed conditions |
| FG001 | Part 1- SAD: Cohort 2 (100mg, Fed) | Participants received a single 100 mg oral dose of ARN-75039 capsules under fed conditions |
| FG002 | Part 1- SAD: Cohort 3 (300mg, Fed and Fasted for FE) | Cohort 3 (food effect cohort) received a single oral dose of ARN 75039 or placebo under fasted conditions no less than 14 days after receiving the first dose under fed conditions |
| FG003 | Part 1- SAD: Cohort 4 (600mg, Fed) | Participants received a single 600mg oral dose of ARN-75039 capsules under fed conditions. |
| FG004 | Part 1- SAD: Cohort 5 (1200mg, Fed) | Participants received a single 1200mg oral dose of ARN-75039 capsules under fed conditions. |
| FG005 | Part 1- SAD: Cohort 6 (2000mg, Fed) | Participants received a single 2000mg oral dose of ARN-75039 capsules under fed conditions. |
| FG006 | Part 1- SAD: Placebo (Fed and Fasted) | Participants received matching placebo capsules containing microcrystalline cellulose administered orally according to the corresponding cohort dosing schedule. |
| FG007 | Part 2- MAD: Cohort 7 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 36 and 24 mg doses, Day 2: 24 mg BID, Days 3-10: 12 mg BID |
| FG008 | Part 2- MAD: Cohort 8 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 75 and 50 mg doses, Day 2: 50 mg BID, Days 3-10: 25 mg BID |
| FG009 | Part 2- MAD: Cohort 9 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 150 and 100 mg doses, Day 2: 100 mg BID, Days 3-10: 50 mg BID |
| FG010 | Part 2- MAD: Cohort 10 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 240 and 160 mg doses, Day 2: 160 mg BID, Days 3-10: 80 mg BID |
| FG011 | Part 2- MAD: Cohort 11 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 360 and 240 mg doses, Day 2: 240 mg BID, Days 3-10: 120 mg BID |
| FG012 | Part 2- MAD: Placebo (Fed) | Participants received matching placebo capsules containing microcrystalline cellulose administered orally according to the corresponding cohort dosing schedule. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Safety Population included all subjects who received at least one dose of study drug (ARN-75039 or placebo). Baseline characteristics were summarized separately for Part 1 (SAD) and Part 2 (MAD) Safety Populations. Overall pooled descriptive statistics across both study parts were not calculated in the CSR for continuous variables (Age, BMI, weight, and height); therefore, overall values are not presented.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1-SAD: Cohort 1 (30mg, Fed) | Participants received a single 30 mg oral dose of ARN-75039 capsules under fed conditions. |
| BG001 | Part 1-SAD: Cohort 2 (100mg, Fed) | Participants received a single 100 mg oral dose of ARN-75039 capsules under fed conditions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at Screening |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Part 1-SAD: Cmax | Maximum Observed Plasma Concentrations of ARN-75039 (Cmax); Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | ng/mL | Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
|
From first dose through the End-of-Study visit: Part 1 (SAD), through Day 15/EOS (14 days after dosing); Food-effect cohort, through Day 29/EOS; Part 2 (MAD), through Day 39/EOS (28 days after the last dose on Day 10).
Adverse events were collected from the first dose through the end-of-study visit. Frequency Threshold set to "zero" due to a small participant pool.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1-SAD: Cohort 1 (30mg, Fed) | Participants received a single 30 mg oral dose of ARN-75039 capsules under fed conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Medical device site reaction | General disorders | MedDRA 25.1 | Systematic Assessment | Medical device site reaction |
Phase 1 safety and pharmacokinetic study in healthy adults; not designed to assess efficacy.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kenneth McCormack, PhD | Arisan Therapeutics | 858-766-0495 | kenm@arisanthera.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 12, 2024 | Jan 20, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 6, 2024 | Jan 21, 2026 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 16, 2024 | Jan 20, 2026 | ICF_002.pdf |
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This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and PK of escalating single and multiple doses of ARN-75039 when administered by the oral route in healthy adult subjects. Six single ascending dose (SAD) cohorts and five multiple ascending dose (MAD) cohorts, with approximately 8 subjects per cohort, will be enrolled to receive study drug or placebo. Within each cohort, the first 2 subjects will be randomized 1:1 to receive ARN-75039 capsules or placebo. After a review of the first 3 days of blinded safety for these subjects by the Medical Monitor, an additional 6 subjects were randomized in a 5:1 (active: placebo) ratio. Each subsequent dose escalation was based on safety data review of the current dose level.
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Central, computer-generated randomization scheme
| Placebo | Drug | Given at frequency and amounts matching ARN- 75039 dosing regimen |
|
|
| Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
| Part 1-SAD: Tmax | PK of ARN-75039 in healthy subjects as assessed by time to reach Cmax (Tmax) towards the determination of the optimal PK dose | Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
| Part 1-SAD: Terminal Half-life | PK of ARN-75039 in healthy subjects as assessed by terminal elimination half-life (T1/2) | Derived from plasma samples collected from Day 1 predose through 336 hours (Day 15/EOS) postdose. |
| Part 1-SAD: AUC | PK of ARN-75039 in healthy subjects as assessed by plasma exposure (AUC), determination of the optimal PK dose | Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
| Part 2-MAD: Cmax0-10h | Maximum Plasma Concentrations of ARN-75039 at 1 and 10 days. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
| Part 2-MAD: Tmax0-10h. | Time to maximum ARN-75039 concentration. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
| Part 2-MAD: AUC0-10h | Area Under the Concentration Time Profile. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| BG002 | Part 1-SAD: Cohort 3 (300mg, Fed and Fasted for Food Effect) | Participants received a single 300 mg oral dose of ARN-75039 under fed conditions on Day 1 and a second 300 mg oral dose under fasted conditions on Day 15 or later after an appropriate washout period to assess the food effect |
| BG003 | Part 1-SAD: Cohort 4 (600mg, Fed) | Participants received a single 600mg oral dose of ARN-75039 capsules under fed conditions. |
| BG004 | Part 1-SAD: Cohort 5 (1200mg, Fed) | Participants received a single 1200mg oral dose of ARN-75039 capsules under fed conditions. |
| BG005 | Part 1-SAD: Cohort 6 (2000mg, Fed) | Participants received a single 2000mg oral dose of ARN-75039 capsules under fed conditions. |
| BG006 | Part 1-SAD: Placebo (Fed and Fasted for Food Effect) | Participants received matching placebo capsules administered according to the corresponding cohort dosing schedule; in the food-effect cohort, placebo was administered under fed conditions on Day 1 and under fasted conditions on Day 15 or later after washout |
| BG007 | Part 2-MAD: Cohort 7 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 36 and 24 mg doses, Day 2: 24 mg BID, Days 3-10: 12 mg BID. |
| BG008 | Part 2: MAD: Cohort 8 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 75 and 50 mg doses, Day 2: 50 mg BID, Days 3-10: 25 mg BID. |
| BG009 | Part 2-MAD: Cohort 9 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 150 and 100 mg doses, Day 2: 100 mg BID, Days 3-10: 50 mg BID. |
| BG010 | Part 2-MAD: Cohort 10 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 240 and 160 mg doses, Day 2: 160 mg BID, Days 3-10: 80 mg BID. |
| BG011 | Part 2-MAD: Cohort 11 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 360 and 240 mg doses, Day 2: 240 mg BID, Days 3-10: 120 mg BID. |
| BG012 | Part 2-MAD: Placebo (Fed) | Participants received matching placebo capsules containing microcrystalline cellulose administered orally according to the corresponding cohort dosing schedule. |
| BG013 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Sex of participants. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race categorized per NIH/OMB classifications. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity categorized per NIH/OMB classifications. | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Body mass index at Screening. | Mean | Standard Deviation | Kg/m^2 |
|
| Weight | Weight at Screening. | Mean | Standard Deviation | kg |
|
| Height | Height at Screening. | Mean | Standard Deviation | cm |
|
| OG001 | Cohort 2 (100mg, Fed) | Participants received a single 100 mg oral dose of ARN-75039 capsules under fed conditions |
| OG002 | Cohort 3 (300mg, Fed) | Participants received a single 300mg oral dose of ARN-75039 under fed conditions, followed by a second dose under fasted conditions after an appropriate washout period to assess the food effect (fed/fasted cross-over). 9 participants completed the fasted period; 8 were included in the PK analysis per SAP (1 excluded due to pre-specified criteria) |
| OG003 | Cohort 3 (300mg, Fasted) | Participants received a single 300mg oral dose of ARN-75039 under fed conditions, followed by a second dose under fasted conditions after an appropriate washout period to assess the food effect (fed/fasted cross-over). 9 participants completed the fasted period; 8 were included in the PK analysis per SAP (1 excluded due to pre-specified criteria) |
| OG004 | Cohort 4 (600mg, Fed) | Participants received a single 600mg oral dose of ARN-75039 capsules under fed conditions. |
| OG005 | Cohort 5 (1200mg, Fed) | Participants received a single 1200mg oral dose of ARN-75039 capsules under fed conditions. |
| OG006 | Cohort 6 (2000mg, Fed) | Participants received a single 2000mg oral dose of ARN-75039 capsules under fed conditions. |
|
|
| Secondary | Part 1-SAD: Tmax | PK of ARN-75039 in healthy subjects as assessed by time to reach Cmax (Tmax) towards the determination of the optimal PK dose | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | h | Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
|
|
|
| Primary | Incidence of Treatment-Emergent Adverse Events (TEAEs) | A treatment-emergent adverse event (TEAE) was defined as any adverse event that began or worsened after administration of the study drug (ARN-75039 or placebo) through the End-of-Study visit. | PK population per SAP; All participants who received ≥ 1 dose of study drug or placebo. | Posted | Count of Participants | Participants | From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS. |
|
|
|
| Primary | Incidence of Treatment-Emergent Serious Adverse Events (TESAEs) | Number of participants with at least one treatment-emergent Serious adverse event (TESAE). A TESAE is any adverse event that starts or worsens after administration of study drug (ARN-75039 or placebo). | The Safety Population included all subjects who received at least one dose of study drug (ARN-75039 or placebo). | Posted | Count of Participants | Participants | From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS. |
|
|
|
| Secondary | Part 1-SAD: Terminal Half-life | PK of ARN-75039 in healthy subjects as assessed by terminal elimination half-life (T1/2) | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | h | Derived from plasma samples collected from Day 1 predose through 336 hours (Day 15/EOS) postdose. |
|
|
|
| Secondary | Part 1-SAD: AUC | PK of ARN-75039 in healthy subjects as assessed by plasma exposure (AUC), determination of the optimal PK dose | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | h*ng/mL | Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose. |
|
|
|
| Secondary | Part 2-MAD: Cmax0-10h | Maximum Plasma Concentrations of ARN-75039 at 1 and 10 days. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | ng/mL | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
|
|
|
| Secondary | Part 2-MAD: Tmax0-10h. | Time to maximum ARN-75039 concentration. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | h | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
|
|
|
| Secondary | Part 2-MAD: AUC0-10h | Area Under the Concentration Time Profile. Pharmacokinetic endpoints included standard noncompartmental parameters following single and multiple ascending oral doses of ARN-75039. The effect of food on ARN-75039 pharmacokinetics was evaluated following administration under fed and fasted conditions. Integrated safety and PK data were used to determine the recommended Phase 2 dose (RP2D) and dosing regimen. | All participants with sufficient post-dose concentrations per SAP. | Posted | Mean | Standard Deviation | h*ng/mL | Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose. |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | Part 1-SAD: Cohort 2 (100mg, Fed) | Participants received a single 100 mg oral dose of ARN-75039 capsules under fed conditions | 0 | 6 | 0 | 6 | 2 | 6 |
| EG002 | Part 1-SAD: Cohort 3 (300mg, Fed) | Participants received a single 300mg oral dose of ARN-75039 under fed conditions, followed by a second dose under fasted conditions after an appropriate washout period to assess the food effect (fed/fasted cross-over). 9 participants completed the fasted period; 8 were included in the PK analysis per SAP (1 excluded due to pre-specified criteria). | 0 | 8 | 0 | 8 | 5 | 8 |
| EG003 | Part 1-SAD: Cohort 3 (300mg, Fasted) | Participants received a single 300mg oral dose of ARN-75039 under fed conditions, followed by a second dose under fasted conditions after an appropriate washout period to assess the food effect (fed/fasted cross-over). 9 participants completed the fasted period; 8 were included in the PK analysis per SAP (1 excluded due to pre-specified criteria). | 0 | 8 | 0 | 8 | 0 | 8 |
| EG004 | Part 1-SAD: Cohort 4 (600mg, Fed) | Participants received a single 600mg oral dose of ARN-75039 capsules under fed conditions. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG005 | Part 1-SAD: Cohort 5 (1200mg, Fed) | Participants received a single 1200mg oral dose of ARN-75039 capsules under fed conditions. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Part 1-SAD: Cohort 6 (2000mg, Fed) | Participants received a single 2000mg oral dose of ARN-75039 capsules under fed conditions. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG007 | Part 1-SAD: Placebo (Fed) | Participants received matching placebo capsules containing microcrystalline cellulose administered orally according to the corresponding cohort dosing schedule. | 0 | 12 | 0 | 12 | 4 | 12 |
| EG008 | Part 1-SAD: Placebo (Fasted) | The onsite pharmacist dispensed the weight of placebo (microcrystalline cellulose) corresponding to the dose drug within the same cohort and encapsulated it in an HPMC capsule prior to dosing. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG009 | Part 2-MAD: Cohort 7 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 36 and 24 mg doses, Day 2: 24 mg BID, Days 3-10: 12 mg BID | 0 | 6 | 0 | 6 | 2 | 6 |
| EG010 | Part 2: MAD: Cohort 8 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 75 and 50 mg doses, Day 2: 50 mg BID, Days 3-10: 25 mg BID | 0 | 6 | 0 | 6 | 2 | 6 |
| EG011 | Part 2-MAD: Cohort 9 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 150 and 100 mg doses, Day 2: 100 mg BID, Days 3-10: 50 mg BID | 0 | 6 | 0 | 6 | 4 | 6 |
| EG012 | Part 2-MAD: Cohort 10 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 240 and 160 mg doses, Day 2: 160 mg BID, Days 3-10: 80 mg BID | 0 | 7 | 0 | 7 | 6 | 7 |
| EG013 | Part 2-MAD: Cohort 11 (Fed) | Participants received multiple oral doses of ARN-75039 administered twice daily (approximately 10 hours apart) for 10 days following a loading dose regimen on Days 1 and 2. Day 1: 360 and 240 mg doses, Day 2: 240 mg BID, Days 3-10: 120 mg BID | 0 | 7 | 0 | 7 | 5 | 7 |
| EG014 | Part 2-MAD: Placebo (Fed) | Participants received matching placebo capsules containing microcrystalline cellulose administered orally according to the corresponding cohort dosing schedule. | 0 | 12 | 0 | 12 | 5 | 12 |
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| Feeling hot | General disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Swelling face | General disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA, version 25.1 | Systematic Assessment | Vessel puncture site bruise |
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| Vessel puncture site pain | General disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Abnormal faeces | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Bowel movement irregularity | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Lip dry | Gastrointestinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Dizziness postural | Cardiac disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Conduction disorder | Cardiac disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Postural orthostatic tachycardia syndrome | Cardiac disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Hypogeusia | Nervous system disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Chalazion | Eye disorders | MedDRA, version 25.1 | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA, version 25.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA, version 25.1 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA, version 25.1 | Systematic Assessment |
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Not provided
Not provided
| AUC 0-∞ |
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| Cmax (day 10) |
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| Tmax0-10h (day 10) |
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| AUC0-10h (day 10) |
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