Investigate the Safety, Tolerability and Pharmacokinetics of FBL-MTX

NCT05117593 | Completed Phase 1

• 1 other identifier: FBL-MTX-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 study to evaluate the safety, tolerability and pharmacokinetics of FBL-MTX in healthy male and female subjects.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; healthy

Outcome Measures

Primary Outcomes (50)

• Change from baseline at each time point of measurement in systolic blood pressure

  Measurements must be recorded from the subject in the supine position after having rested for at least 5 min

  From study treatment administration up to end of study, an average of 1month

• Change from baseline at each time point of measurement in diastolic blood pressure

  Measurements must be recorded from the subject in the supine position after having rested for at least 5 min

  From study treatment administration up to end of study, an average of 1month

• Change from baseline at each time point of measurement in pulse rate

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in hemoglobin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in red cell count

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in hematocrit

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in mean corpuscular volume

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in mean corpuscular hemoglobin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in mean corpuscular hemoglobin concentration

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in red cell distribution width

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in white cell count with differential

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in platelet count

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in mean platelet volume

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in AST

  Measurement of aspartate aminotransferase

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in clinical ALT

  Measurement of alanine aminotransferase

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in gamma-glutamyltransferase (GGT)

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in alkaline phosphatase (ALP)

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in total bilirubin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in indirect bilirubin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in direct bilirubin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in lactate dehydrogenase (LDH)

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in creatinine

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in urea

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in urate

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in glucose

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in cholesterol

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in triglycerides

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in sodium

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in potassium

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in chloride

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in calcium

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in protein

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in albumin

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in creatine kinase (CK)

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in creatinine clearance

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in glucose in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in bilirubin in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in ketone in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in specific gravity

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in hemoglobin in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in pH in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in protein in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in urobilinogen

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in nitrite in urine

  Urinalysis test

  From study treatment administration up to end of study, an average of 1 month

• Change from baseline at each time point of measurement in heart rate

  From study treatment administration up to the end of study, an average of 1 month

• Change from baseline at each time point of measurement in QT interval corrected with Bazett's formula

  From study treatment administration up to the end of study, an average of 1 month

• Change from baseline at each time point of measurement in QT interval corrected with Fridericia's formula (QTcF)

  From study treatment administration up to the end of study, an average of 1 month

• Treatment-emergent AEs

  From study treatment administration up to the end of study, an average of 1 month

• Treatment-emergent SAEs

  From study treatment administration up to the end of study, an average of 1 month

• Treatment-emergent AEs leading to premature study discontinuation.

  From study treatment administration up to the end of study, an average of 1 month

Secondary Outcomes (8)

• Maximum plasma concentration (Cmax)

  Multiple pharmacokinetic sampling at predefined timepoints from Day 1 (pre-dose) up to Day 7.

• Time to reach Cmax (tmax).

  Multiple pharmacokinetic sampling at predefined timepoints from Day 1 (pre-dose) up to Day 7.

• Area under the concentration-time curve (AUC) from time zero to last measurable plasma concentration (AUC0-t)

  Multiple pharmacokinetic sampling at predefined timepoints from Day 1 (pre-dose) up to Day 7.

• AUC from time zero to infinity (AUC0-∞)

  Multiple pharmacokinetic sampling at predefined timepoints from Day 1 (pre-dose) up to Day 7.

• Terminal elimination rate constant (λz).

  Multiple pharmacokinetic sampling at predefined timepoints from Day 1 (pre-dose) up to Day 7.

Study Arms (2)

FBL-MTX

EXPERIMENTAL

A single dose of FBL-MTX will be administered by slow intravenous injection in the morning, under fasted conditions. A maximum of 4 dose levels (0.1 mg, 0.33 mg, 1 mg and 2.5 mg) are pre-planned.

Drug: FBL-MTX

Placebo

PLACEBO COMPARATOR

A single dose of placebo will be administered by slow injection in the morning, under fasted conditions.

Drug: Placebo

Interventions

FBL-MTX DRUG

FBL-MTX is available as sterile liposomal dispersion for injection at nominal dose strength of 1 mg/mL of methotrexate free base. The dose of 0.1 mg was selected as starting dose in the present study. Three subsequent FBL-MTX dose levels are pre-planned: 0.33 mg, 1 mg and 2.5 mg.

FBL-MTX

Placebo DRUG

Placebo will consist of sterile saline 0.9% NaCl solution.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Healthy male or female subjects aged between 18 and 55 years (inclusive) at Screening.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
• Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the study requirements.
• Systolic blood pressure (SBP) 100-140 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured on the same arm after ≥5 min in the supine position, at Screening and on Day -1.
• Estimated glomerular filtration rate calculated using the Cockcroft-Gault equation ≥ 90 mL/min at Screening.
• A female subject of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 and must agree to consistently and correctly use (from Screening, during the entire study, and for at least 6 months after investigational product administration) a highly effective method of contraception with a failure rate of ≤1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must be initiated at least 1 month before the treatment administration.
• A female subject of non-childbearing potential, must be post-menopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a follicle stimulating hormone \[FSH\] test), or must have a medical history of previous bilateral salpingectomy, bilateral salpingo-oophorectomy, hysterectomy, premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, or uterine agenesis.
• A male subject must use adequate contraception (e.g., condom) from investigational product administration up to at least 6 months after, unless he is vasectomized or sexually inactive. In addition, the subject must ensure that his female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception with a failure rate of ≤1% per year.
• A male subject must agree to refrain from donation of semen from investigational product administration up to at least 6 months after.

You may not qualify if:

• Previous exposure to FBL-MTX.
• Known hypersensitivity to MTX or any other FBL-MTX components.
• Clinically relevant findings on physical examination at Screening or on Day -1.
• Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in a supine position, at Screening or on Day -1.
• Clinically relevant abnormalities on chest X-ray at Screening.
• Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis) at Screening or on Day -1.
• Pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia.
• QTc \> 450ms in male and \> 470ms in female.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above the normal range.
• Any medical condition, acute, ongoing, recurrent or chronic, that presents a potential risk to the participant and/or that may compromise the objectives of the study.
• History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the distribution, metabolism, or excretion of the investigational product.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator.
• History of tuberculosis.
• Presence of chronic or acute bacterial or viral infection.
• History or presence of an autoimmune disorder.

Sponsors & Collaborators

• SOLFARCOS - Pharmaceutical and Cosmetic Solutions Ltd: lead

Study Sites (1)

BlueClinical Phase I

Porto, 4250-449, Portugal

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A maximum of 4 dose levels (0.1 mg, 0.33 mg, 1 mg and 2.5 mg) is preplanned to be investigated in separate sequential cohorts. Each cohort will consist of 8 healthy male and female subjects (3 subjects of either sex on FBL-MTX, 1 of either sex on placebo).

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: November 11, 2021
• Study Start: June 28, 2021
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: November 22, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)