Phase 1 Study on Bioavailability, Food Effect, and Drug-Drug Interaction of ALG-097558 Tablets in Healthy Volunteers

NCT06945276 | Completed Phase 1 FDA Drug

• 1 other identifier: 24-0026
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this multi-part Phase 1 study is to evaluate the drug-drug interaction (DDI) potential of ALG-097558 via co-administration with a P-gp substrate (dabigatran) and a CYP3A4 inhibitor/P-gp inhibitor (itraconazole). In addition, this study will evaluate the relative bioavailability and food effect of a new tablet formulation for ALG-097558. This study consists of 3 parts, all conducted in healthy volunteers (HV). Study Parts A and B are designed to assess the perpetrator or victim DDI risk of ALG-097558 mediated by CYP/P-gp interactions in healthy adult subjects. Part A will evaluate the potential impact of itraconazole, a CYP3A potent inhibitor, while Part B will investigate the potential impact of ALG-097558 (perpetrator) on dabigatran etexilate, a P-gp transporter substrate. Study Part C is designed to study the bioavailability of a new formulation of the ALG-097558 tablet and the food effect on this tablet. This study has one primary objective for each part of the study. For Part A: to evaluate the effect of a CYP3A4 inhibitor/Pg-p inhibitor, itraconazole, on the pharmacokinetics (PK) of ALG-097558 and the metabolite, ALG-097730. For Part B: to evaluate the effect of multiple doses of ALG-097558 on the pharmacokinetics of a P-gp substrate, dabigatran. For Part C: to evaluate the relative bioavailability of 2 different tablet formulations of ALG-097558 and effect of food on the pharmacokinetics of ALG-097558 and the metabolite, ALG-097730.

Conditions

COVID-19

Keywords

ALG-097558; Dabigatran; Drug-Drug Interaction; Healthy Subjects; Interventional; Itraconazole; SARS-CoV-2; Tablet Formulation

Outcome Measures

Primary Outcomes (7)

• Area under the concentration-time curve from time zero to infinity [extrapolated] (AUC0-inf)

  Up to Day 10

• Area under the concentration-time curve from time zero to the last measurable concentration (AUClast)

  Up to Day 10

• Elimination half-life (t1/2)

  Up to Day 10

• Initial concentration (C0)

  Up to Day 10

• Maximum observed concentration (Cmax)

  Up to Day 10

• Minimum observed concentration (Cmin)

  Up to Day 10

• Time of observed maximum concentration (Tmax)

  Up to Day 10

Secondary Outcomes (1)

• Incidence of adverse events

  Up to Day 10

Study Arms (5)

Part A Arm

EXPERIMENTAL

A single-blind oral placebo dose will be administered on Day 1. On Day 2, an open-labeled single oral dose of 300 mg of ALG-097558 will be administered as a spay-dried dispersion (SDD) tablet, followed by a washout period of at least 2 days. On Day 4-10 participants will receive a daily oral dose of Itraconazole 200 mg. A single oral dose of matching placebo (SDD tablet) for ALG-097558 will be given on Day 6, and a single oral dose of 300 mg of ALG-097558 SDD tablet will be given on Day 7. (N=12)

Drug: ALG-097558; Drug: Itraconazole; Other: Placebo

Part B Arm

EXPERIMENTAL

A single oral dose of 75 mg of dabigatran will be administered on Day 1, in a fasted stated, followed by a washout period of at least 3 days. Participants will then receive multiple oral doses of 600 mg of ALG-097558 Q12H as a spray-dried dispersion (SDD) tablet on Days 4-5, in a fasted state. A single oral dose of 75 mg of dabigatran will be given on Day 5, in a fasted state. (N=24)

Drug: ALG-097558; Drug: Dabigatran

Part C Sequence 1 Arm

EXPERIMENTAL

A single oral dose of 600 mg of ALG-097558, in a spray-dried dispersion (SDD) tablet will be administered in the fasted state, followed by a 3-day washout period. On Day 4, a single oral dose of 600 mg of ALG-097558, in a conventional tablet will be administered in the fasted state, followed by another 3-day washout period. On Day 7, a single oral dose of 600 mg of ALG-097558, in a conventional tablet will be administered in the fed state. (N=5)

Drug: ALG-097558

Part C Sequence 2 Arm

EXPERIMENTAL

A single oral dose of 600 mg of ALG-097558, in a conventional tablet will be administered in the fasted state, followed by a 3-day washout period. On Day 4, a single oral dose of 600 mg of ALG-097558 in a conventional tablet will be administered in the fed state, followed by another 3-day washout period. On Day 7, a single oral dose of 600 mg of ALG-097558, in a spray-dried dispersion (SDD) tablet will be administered in the fasted state. (N=5)

Drug: ALG-097558

Part C Sequence 3 Arm

EXPERIMENTAL

A single oral dose of 600 mg of ALG-097558, in a conventional tablet will be administered in the fed state, followed by a 3-day washout period. On Day 4, a single oral dose of 600 mg of ALG-097558 in a spray-dried dispersion (SDD) tablet will be administered in the fasted state, followed by another 3-day washout period. On Day 7, a single oral dose of 600 mg of ALG-097558, in a conventional tablet will be administered in the fasted state. (N=5)

Drug: ALG-097558

Interventions

ALG-097558 DRUG

A selective, reversible, and potent inhibitor of the SARS-CoV-2 3CLpro with pan-coronavirus activity

Part A Arm; Part B Arm; Part C Sequence 1 Arm; Part C Sequence 2 Arm; Part C Sequence 3 Arm

Dabigatran DRUG

A direct thrombin inhibitor approved for the treatment and prevention of blood clots to reduce the risk of stroke

Part B Arm

Itraconazole DRUG

A substrate and strong dual inhibitor of CYP3A4/P-glycoprotein (P-gp)

Part A Arm

Placebo OTHER

Placebo

Part A Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is able to read the written informed consent, states willingness to comply with all study procedures, and is anticipated to be available for all study visits.
• Male or female adults between 18 and 65 years of age, inclusive.
• Female participants must either be postmenopausal\*, permanently sterile\*\*, or of childbearing potential with acceptable birth control methods\*\*\*.
• \*Postmenopausal: a postmenopausal state is defined as no menses for at least 12 months without an alternative medical explanation, confirmed by a high follicle-stimulating hormone (FSH) level in the postmenopausal range at screening. NOTE: If there is a question about menopausal status in women on hormone replacement therapy (HRT), the woman will be required to use one of the protocol-defined non-estrogen-containing hormonal highly effective contraceptive methods if she wishes to continue HRT during the study.
• \*\*Permanently sterile: methods include hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral tubal occlusion.
• Women of childbearing potential (WOCBP): are only eligible if they and any non-sterile, male sexual partners agree to use protocol-defined highly effective (dependent or independent) contraceptive therapy, from the start of dosing until at least 90 days after the last dose. Acceptable method of contraception, hormonal contraceptives (e.g., oral, injectable, implantable, insertable, and transdermal patch), intrauterine device (with or without hormones), or double-barrier method (e.g., condom and spermicide) for 30 days prior to Screening, during the study, and for 90 days following the last administration of investigational product (IP). WOCBP must also agree to refrain from egg donations during the study and for at least 90 days following the last administration of IP.
• Male participants who must agree to wear a condom with spermicide during sexual intercourse.\*
• \*These contraceptive measures must be implemented, at a minimum, from the start of dosing until at least 90 days after the last dose. Male volunteers must agree not to donate sperm during the study and for 90 days following the last administration of IP.
• Participants must have a body mass index (BMI) of 18.0 to 32.0 kg/m\^2, extremes included.
• Participants must be nonsmokers for at least 3 months prior to randomization/enrollment.
• \*Criteria includes: heart rate between 40 and 100 beats per minute \[bpm\], extremes included; QT interval corrected for heart rate (QTc) according to Fridericia's formula (QTcF) \</= 450 ms (males) or \</= 470 ms (females); QRS interval \</=120 ms; PR interval \>/=110 to \</=220 ms; and in addition to fulfilling the above ECG criteria, ECG morphology must have no clinically significant abnormalities observed.
• Participants must be deemed to be in good overall health by the Investigator on the basis of a medical evaluation\* performed at Screening.
• \*Medical evaluation that includes the absence of any clinically significant abnormality and includes a physical examination, medical history, vital signs, and the results of blood chemistry, blood coagulation and hematology tests, and urinalysis.
• Subject must be willing and able to adhere to the Prohibited Medication requirements and Special Precautions as specified in the protocol.

You may not qualify if:

• Participants with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose risk in administering study drug to the subject.\* \*Additionally illnesses that could prevent, limit, or confound the protocol specified assessments or study results' interpretation. This may include, but is not limited to, renal, cardiac, vascular, pulmonary, gastrointestinal, hepatologic, endocrine, neurologic, dermatologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances.
• Participants with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome or clinical evidence at screening of significant or unstable cardiac disease.\*
• Participants with a history of clinically significant drug allergy such as, but not limited to, sulfonamides or drug allergy witnessed in previous studies with experimental drugs.
• Participants with a recent (within 1 year of randomization/enrollment) history of use of amphetamines, barbiturates, narcotic or other drugs of abuse/recreational drug use.\*
• Excessive use of alcohol defined as regular consumption of \>/=14 standard drinks/week .\*
• \*For current definition of a standard drink, refer to the National Institute on Alcohol Abuse and Alcoholism website.
• Unwilling to abstain from alcohol use for 1 week prior to start of study through end of study follow up.
• Positive results for urine drug screen for barbiturates, opiates, amphetamines, methadone, cocaine, benzodiazepines, or cannabinoids, alcohol or cotinine test at screening and Day - 1.
• Participants with current viral infections.\*
• \*Viral infections include the following:
• Hepatitis A virus infection (confirmed by hepatitis A antibody immunoglobulin M \[IgM\]).
• Hepatitis B infection defined as presence of HBsAg or HBV core antibody.
• Hepatitis C virus (HCV) infection (confirmed by HCV antibody and/or HCV RNA). Participants who have been treated and achieved sustained virologic response \>/=6 months prior to screening with HCV RNA \< Lower limit of quantitation (LLOQ), target not detected, remain eligible.
• Hepatitis E virus: Anti-HEV IgM-positive and/or detectable HEV RNA level (only applies to participants with history of living or traveling to an HEV epidemic area within 90 days of screening).
• Human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Dr. Vince Clinical Research

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

Dabigatran; Itraconazole

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Triazoles; Azoles; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are only masked in Part A. Parts B and Part C are open label.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Part A and B are single group. Part C is crossover.

Study Record Dates

• First Submitted: April 18, 2025
• First Posted: April 25, 2025
• Study Start: May 13, 2025
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-04-18

Locations

US (1)