Safety, Tolerability and Pharmacokinetics of Benfo-Oxythiamine (B-OT) in Healthy Volunteers

NCT07450833 | Completed Phase 1 Results

• 2 other identifiers: BV-01-1012021-005616-60
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial was to learn about the safety and tolerability of an investigational drug called Benfo-oxythiamine (B-OT) in healthy male volunteers. Researchers are studying B-OT to see if it might be used to treat infectious diseases and cancer. This study also looked at how the drug enters, moves through, and leaves the body. The main questions it aimed to answer were:

• Is B-OT safe for humans to take?
• What medical problems do participants have when taking B-OT?
• How much of the drug gets into the blood? Participants:
• Took B-OT capsules by mouth either once (single dose group) or once a day for 7 days (multiple dose group).
• Stayed in the clinic for several days (4 to 8 nights) for close monitoring.
• Gave blood and urine samples for laboratory tests;
• Had physical exams, heart rhythm checks (ECG), and vital sign checks (blood pressure, heart rate, breathing rate, and temperature).

Conditions

Healthy Volunteers

Keywords

Benfo-oxythiamine (B-OT); Oxythiamine; Phase I; Pharmacokinetics; Safety; Transketolase Inhibitor; SARS-CoV-2; COVID-19; Prodrug; Thiamine antagonist; Metabolic inhibitor; First-in-human (FIH); Single Ascending Dose (SAD); Multiple Ascending Dose (MAD); Healthy volunteers; Cancer metabolism; Oncology; Metabolic Targets; Solid Tumors; TKTL1; Transketolase

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Assessment of safety and tolerability through the collection of treatment-emergent adverse events (TEAEs). A TEAE is defined by its timing: it is any adverse event that occurs, or an existing condition that worsens in severity, after the start of study drug administration, regardless of its intensity. Unit of measure: Number of participants.

  From informed consent through Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

• Number of Participants With Serious Adverse Events (SAEs)

  Assessment of safety and tolerability through the collection of serious adverse events (SAEs). An SAE is defined by its severe clinical consequences: it is any event that results in death, is life-threatening, requires inpatient hospitalization, results in persistent disability, or requires medical intervention to prevent these outcomes. Unit of measure: Number of participants.

  From informed consent through Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

• Number of Participants With Clinically Significant Abnormalities in Safety Laboratory Assessments

  Evaluation of the number of participants experiencing clinically significant abnormal changes compared to baseline in Hematology, Biochemistry, Coagulation, and Urinalysis parameters. Unit of measure: Number of participants.

  Baseline (Day -1) and up to Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Evaluation of the number of participants with clinically significant abnormal changes compared to baseline in vital sign measurements, including systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature. Unit of measure: Number of participants.

  Baseline (Day -1) and up to Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

• Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)

  Evaluation of the number of participants with clinically significant abnormal findings in 12-lead ECG measurements, including PR interval, QRS duration, QT interval, and QTcF (Fridericia correction) compared to baseline. Unit of measure: Number of participants.

  Baseline (Day 1 pre-dose) and up to Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

• Number of Participants With Clinically Significant Abnormal Physical Examination Findings

  Evaluation of the number of participants with clinically significant abnormal findings detected during physical body system assessments compared to baseline. Unit of measure: Number of participants.

  Baseline (Screening) and up to Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

Secondary Outcomes (24)

• Single Ascending Dose (SAD): Maximum Plasma Concentration (Cmax) of Oxythiamine

  Pre-dose and at multiple time points up to 168 hours post-dose on Day 1

• Single Ascending Dose (SAD): Area Under the Curve (AUC0-t) of Oxythiamine

  Pre-dose and at multiple time points up to 168 hours post-dose on Day 1

• Single Ascending Dose (SAD): Area Under the Curve Infinity (AUC0-inf) of Oxythiamine

  Pre-dose and at multiple time points up to 168 hours post-dose on Day 1

• Single Ascending Dose (SAD): Time to Maximum Concentration (Tmax) of Oxythiamine

  Pre-dose and at multiple time points up to 168 hours post-dose on Day 1

• Single Ascending Dose (SAD): Terminal Elimination Half-Life (t1/2) of Oxythiamine

  Pre-dose and at multiple time points up to 168 hours post-dose on Day 1

Other Outcomes (1)

• Exploratory: Transketolase Activity

  Pre-dose and multiple time points up to Day 8 (Single Ascending Dose) or Day 14 (Multiple Ascending Dose)

Study Arms (9)

SAD Cohort 1

EXPERIMENTAL

Participants receive a single oral dose of 0.5 mg Benfo-oxythiamine on Day 1

Drug: Benfo-oxythiamine

SAD Cohort 2

EXPERIMENTAL

Participants receive a single oral dose of 1 mg Benfo-oxythiamine on Day 1

Drug: Benfo-oxythiamine

SAD Cohort 3

EXPERIMENTAL

Participants receive a single oral dose of 2 mg Benfo-oxythiamine on Day 1

Drug: Benfo-oxythiamine

SAD Cohort 4

EXPERIMENTAL

Participants receive a single oral dose of 3 mg Benfo-oxythiamine on Day 1

Drug: Benfo-oxythiamine

SAD Cohort 5

EXPERIMENTAL

Participants receive a single oral dose of 5 mg Benfo-oxythiamine on Day 1

Drug: Benfo-oxythiamine

MAD Group 1

EXPERIMENTAL

Participants receive 1 mg Benfo-oxythiamine orally once daily for 7 consecutive days

Drug: Benfo-oxythiamine

MAD Group 2

EXPERIMENTAL

Participants receive 2 mg Benfo-oxythiamine orally once daily for 7 consecutive days

Drug: Benfo-oxythiamine

MAD Group 3

EXPERIMENTAL

Participants receive 3 mg Benfo-oxythiamine orally once daily for 7 consecutive days

Drug: Benfo-oxythiamine

MAD Group 4

EXPERIMENTAL

Participants receive 5 mg Benfo-oxythiamine orally once daily for 7 consecutive days

Drug: Benfo-oxythiamine

Interventions

Benfo-oxythiamine DRUG

Benfo-oxythiamine (B-OT) is an orally bioavailable prodrug of the thiamine antagonist oxythiamine, formulated as hard gelatin capsules (0.5 mg or 3 mg strengths) containing powder-in-capsule. Upon ingestion, it releases oxythiamine to inhibit transketolase enzymes. In the Single Ascending Dose (SAD) part, B-OT is administered as a single oral dose on Day 1. Dose levels are 0.5 mg, 1 mg, 2 mg, 3 mg, and 5 mg. In the Multiple Ascending Dose (MAD) part, B-OT is administered orally once daily for 7 consecutive days. Dose levels are 1 mg, 2 mg, 3 mg, and 5 mg. Administration occurs after an overnight fast of at least 10 hours with 240 mL of water.

Also known as: B-OT, Benfo-oxythiamine phosphate monosodium

MAD Group 1; MAD Group 2; MAD Group 3; MAD Group 4; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3; SAD Cohort 4; SAD Cohort 5

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed and dated informed consent form.
• Subjects capable to understand the purposes and risks of the study.
• Male volunteers willing to comply with contraception requirements.
• Aged 18-60 years, inclusive.
• Healthy participants, as determined by screening assessments and Principal Investigator's judgment (absence of active/chronic disease).
• Body Mass Index (BMI) of 18-30 kg/m² inclusive.
• Male participants with female partners of childbearing potential must agree to be abstinent or use a male condom plus partner use of a contraceptive method.

You may not qualify if:

• Clinically relevant history of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, or connective tissue disorders.
• Fridericia's correction factor for QT (QTcF) \> 450 ms or history of QT interval prolongation.
• Acute gastrointestinal symptoms at screening/admission.
• Any abnormal laboratory value of Grade 2 or higher considered clinically significant.
• Values ≥ 10% above upper limit of normal for ALT, AST, Alkaline Phosphatase, Creatinine, or Urea.
• Clinically relevant surgical history.
• History of relevant drug hypersensitivity, alcoholism, or drug abuse.
• Significant infection or known inflammatory process.
• Use of prescription/non-prescription medicines within 2 weeks of admission.
• Receipt of investigational drug within 30 days prior to screening.
• Use of tobacco/nicotine products within 3 months of screening.
• Positive alcohol or drug screen.
• Blood donation within 3 months prior to screening.
• Vaccinated with a Covid-19 vaccine within 2 weeks prior to screening.

Sponsors & Collaborators

• Benfovir AG: lead

Study Sites (1)

Diagnostics and Consultation Center (DCC) Convex EOOD

Sofia, Bulgaria

Location

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• Beielstein AC, Izquierdo E, Blakemore S, Nickel N, Michalik M, Chawan S, Brinker R, Bartel HH, Vorholt D, Albert L, Nolte JL, Linke R, Costa Picossi CR, Saiz J, Picard F, Florin A, Meinel J, Buttner R, Diefenhardt P, Brahler S, Villasenor A, Winkels H, Hallek M, Kruger M, Barbas C, Pallasch CP. Macrophages are activated toward phagocytic lymphoma cell clearance by pentose phosphate pathway inhibition. Cell Rep Med. 2024 Dec 17;5(12):101830. doi: 10.1016/j.xcrm.2024.101830. Epub 2024 Nov 26.

  PMID: 39603243 BACKGROUND

MeSH Terms

Conditions

COVID-19; Neoplasms; Korsakoff Syndrome

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; Memory Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kathrin Riepe, Leader Clinical Development
• Organization: benfovir AG

riepe@benfovir.com

+49 173 450 87 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: March 5, 2026
• Study Start: March 1, 2022
• Primary Completion: November 21, 2022
• Study Completion: November 21, 2022
• Last Updated: April 20, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)