A Phase 1, Pharmacokinetics of the MMP-12 Inhibitor FP-025 After Multiple Oral Ascending Doses in Healthy Subjects

NCT03304964 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: FP02C-17-001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, phase I study consisting of 2 parts. The first part is a multiple ascending dose (MAD) part with a randomized, double-blind, placebo-controlled design in 3 treatment groups of 8 subjects (6 active; 2 placebo). The second part is a food effect (FE) part with a randomized, open-label, 2-period, 2-way crossover, single dose design in 8 subjects.

Conditions

Healthy

Keywords

FP-025, MMP-12 inhibitor

Outcome Measures

Primary Outcomes (2)

• Treatment-emergent, AEs, SAEs and ECG abnormalities up to end-of-study (EOS).

  Safety evaluation will study the adverse event (AE) profile, clinical laboratory safety tests, vital signs, and ECG monitoring

  17 days ± 2 days

• Change from baseline for vital sign, ECG parameters [(QTc = QT/RR1/3.)], and clinical laboratory test for scheduled time point up to end-of-study (EOS).

  Safety evaluation will study the adverse event (AE) profile, clinical laboratory safety tests, vital signs, and ECG monitoring. The ECG parameter QTc will be calculated according to Fridericia's correction using the ECG parameters QT interval (QT) and RR recorded. QTc (msec) = QT (msec)/RR (sec)1/3. QT msec will be calculated with RR sec to arrive at one reported value for QTc.

  17 days ± 2 days

Secondary Outcomes (26)

• Analysis of the plasma concentration-time on Day 1 (Cmax)

  17 days ± 2 days

• Analysis of the plasma concentration-time on Day 1 (Tmax)

  17 days ± 2 days

• Analysis of the plasma concentration-time on Day 1 (AUC0-12)

  17 days ± 2 days

• Analysis of the plasma concentration-time on Day 1 (AUC0-24)

  17 days ± 2 days

• Analysis of the plasma concentration-time on Day 1 (AUC0-inf)

  17 days ± 2 days

Study Arms (5)

100 mg FP-025 (b.i.d)

EXPERIMENTAL

Drug: FP-025 (MMP-12 inhibitor)

200 mg FP-025 (b.i.d.)

EXPERIMENTAL

Drug: FP-025 (MMP-12 inhibitor)

400 mg FP-025 (b.i.d)

EXPERIMENTAL

Drug: FP-025 (MMP-12 inhibitor)

200 mg FP-025 (single dose; fasted)

EXPERIMENTAL

Drug: FP-025 (MMP-12 inhibitor)

200 mg FP-025 (single dose; fed condition)

EXPERIMENTAL

Drug: FP-025 (MMP-12 inhibitor)

Interventions

FP-025 (MMP-12 inhibitor) DRUG

Treatment A: 14 oral doses of 100 mg FP-025 (n=6) or placebo (n=2) in 8 days.

100 mg FP-025 (b.i.d)

Eligibility Criteria

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

You may qualify if:

• Males aged ≥18 and ≤65 years or postmenopausal females aged ≥18 and ≤65 years, with a BMI ≥18 kg/m2 and ≤30 kg/m2. Female subjects must be of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy or bilateral oophorectomy; or as post-menopausal females defined as 12 months amenorrhoea and follicle stimulating hormone (FSH) levels \>40 IU/L.
• A resting pulse ≥40 bpm and ≤100 bpm at screening and on Day -1.
• A resting systolic blood pressure of ≤150 mmHg and a resting diastolic blood pressure of ≤95 mmHg at screening and on Day -1.
• Baseline laboratory test values within reference ranges based on the blood and urine samples taken at screening and on Day -1. Out of normal ranges values may be accepted by the Investigator, if not clinically significant.
• The subject is, in the opinion of the Investigator, generally healthy based on assessment of medical history, physical examination, vital signs, electrocardiogram (ECG), and the results of the haematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
• Male subjects must use adequate contraception, if applicable, during the study and until 3 months after completion of the study.
• Subjects participating in the FE part of the study must be willing and able to consume the entire high-fat, high-calorie breakfast in the designated timeframe.
• Signed Informed Consent prior to any study related procedures.
• Ability to communicate well with the Investigator, in the local language, and to understand and comply with the requirements of the study.

You may not qualify if:

• The subject has taken prescription or non-prescription medication, herbal remedies, vitamins or minerals within 2 weeks prior to the first dose of study product (or within 5 half-lives prior to the first dose of study product for any medication ingested, whichever is longer).
• The subject has a substance abuse-related disorder or has a history of drug, alcohol and/or substance abuse deemed significant by the investigator.
• The subject has taken any investigational products within 60 days prior to the first dose of study product.
• The subject has a history of severe drug allergy or hypersensitivity or food allergy.
• The subject has a history or presence of any clinically significant immunological, cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (in particular diabetes or pre-diabetes), haematological, dermatological, venereal, neurological, chronic infectious or psychiatric disease or other major disorder.
• The subject has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study product.
• The subject has a history of abdominal surgery (excluding laparoscopic cholecystectomy or uncomplicated appendectomy) or thoracic or non-peripheral vascular surgery within 6 months prior to the first dose of study product.
• The subject has any concurrent illness that may affect the particular target or absorption, distribution, and elimination of the study product.
• The subject has had a clinically significant illness within 4 weeks prior to the first dose of study product.
• The subject has had surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study product.
• The subject has donated blood more than 250 mL within 2 months prior to the first dose of study product.
• The subject has tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV).
• The subject is a current smoker or uses other nicotine containing products. Ex-smokers must have ceased smoking at least 6 months prior to the first dose of study product.
• The subject has tested positive at screening or on Day -1 for drugs of abuse or alcohol.
• A female subject who has a positive urine pregnancy test at screening or on Day -1.

Sponsors & Collaborators

• Foresee Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

QPS Netherlands B.V.

Petrus Campersingel 123, Provincie Groningen, 9713 AG, Netherlands

Location

Related Publications (1)

• Abd-Elaziz K, Voors-Pette C, Wang KL, Pan S, Lee Y, Mao J, Li Y, Chien B, Lau D, Diamant Z. First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects. Clin Drug Investig. 2021 Jan;41(1):65-76. doi: 10.1007/s40261-020-00981-9. Epub 2020 Dec 17.

  PMID: 33331980 DERIVED

MeSH Terms

Interventions

FP-025

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: MAD part (Part 1) - double-blind; FE part (Part 2) - open-label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: MAD part (Part 1) - sequential multiple ascending doses; FE part (Part 2) - crossover food effect after single dose administration

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: October 9, 2017
• Study Start: July 21, 2017
• Primary Completion: June 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 13, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)