Ascending Dose Tolerability Trial and PK Assessment in Healthy Volunteers After Single & Multiple Oral Intake of DF2755A

NCT04803396 | Terminated Phase 1 Results

• 2 other identifiers: BPS01152016-003629-41
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective:

• To evaluate the tolerability and safety of ascending single doses of DF2755A in healthy adult male and female volunteers. Secondary Objectives:
• To determine the pharmacokinetics parameters of DF2755A
• To establish a dose concentration-response relationship over a wide range of doses in order to select a narrower range of dose and dosing regimen to be subsequently studied in patients after single administration
• To evaluate the effect of ascending single doses on the pharmacodynamics parameters
• To compare metabolites pathway in Human with the one observed in animals Please note that the study has been closed after Part A (single ascending doses), so all the objectives were revised accordingly.

Conditions

no Condition

Keywords

Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events by Severity

  Adverse Event (AE), is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment/product. Serious Adverse Event or Reaction, is any untoward medical occurrence, that: * Results in death; * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability or incapacity * an important medical event/reaction that may jeopardize the patient and require medical / surgical intervention to prevent one of the outcomes above. Any AE (including laboratory test abnormalities, intercurrent illnesses or injuries, and/or study procedures related AE) reported spontaneously by the subjects, or observed by the Investigator, was recorded according to the procedures in force at Eurofins Optimed.

  Throughout the study, up to Day 4

Secondary Outcomes (17)

• Cmax of DF2755A

  Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

• Tmax

  Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

• t1/2

  Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

• AUC0-t

  Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

• AUC 0-inf

  Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Study Arms (5)

Placebo RS/PKS/PDS/SS

PLACEBO COMPARATOR

Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.

Other: Placebo

DF2755A 50 mg - RS/PKS/PDS/SS

EXPERIMENTAL

The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.

Drug: DF2755A

DF2755A 150 mg - RS/PKS/PDS/SS

EXPERIMENTAL

The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.

Drug: DF2755A

DF2755A 300 mg - RS/PKS/PDS/SS

EXPERIMENTAL

The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.

Drug: DF2755A

DF2755A 600 mg - RS/PKS/PDS/SS

EXPERIMENTAL

The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.

Drug: DF2755A

Interventions

DF2755A DRUG

DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) but not performed (repeated oral administration from Day 1 to Day 14).

Also known as: allosteric inhibitor of CXCR1/2

DF2755A 150 mg - RS/PKS/PDS/SS; DF2755A 300 mg - RS/PKS/PDS/SS; DF2755A 50 mg - RS/PKS/PDS/SS; DF2755A 600 mg - RS/PKS/PDS/SS

Placebo OTHER

Single oral dose administration on D1

Also known as: Matching placebo

Placebo RS/PKS/PDS/SS

Eligibility Criteria

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

You may qualify if:

• Healthy male subject, aged between 18 and 55 years inclusive;
• Healthy female subject infertile or in post menopause for at least two years, aged between 18 and 60 years inclusive;
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weight ≤ 90kg;
• Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination);
• Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position:
• mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg or 150mmHg for subject \> 45 years,
• mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg,
• bpm ≤ HR ≤ 100 bpm, Or considered NCs by investigators;
• Smoker \< 5cigarettes per day who stop totally during the study;
• Normal ECG recording on a 12-lead ECG at the screening visit:
• \< PR \< 210 ms,
• QRS \< 120 ms,
• QTcf ≤ 430 ms for male and \< 450 ms for female,
• No sign of any trouble of sinusal automatism, Or considered NCs by investigators;
• Normal oral temperature;

You may not qualify if:

• Subject has had a clinically significant illness in the six weeks before screening in the opinion of the Investigator.
• Subject has had a serious adverse reaction or significant hypersensitivity to any drug, has a known clinically significant allergy to anti-inflammatory drugs or chemically related compounds or has a clinically significant allergy to drugs, foods or other materials (in the opinion of the Investigator). However, subjects with mild hayfever may be included in the study.
• Subject has used prescription medication in the 14 days prior to dosing or over-the-counter preparations for 7 days prior to dosing (including vitamin supplements and herbal remedies), with the exception of paracetamol which was allowed during the study (maximum 500 mg per administration, total daily dose maximum 2 grams).
• Subject has a significant history of drug/solvent abuse or a positive drugs of abuse (DOA) test at any time during the study.
• Subject has a history of alcohol abuse in the last 5 years or currently drinks in excess of 21 and 14 units per week for males and female, respectively, or has a positive alcohol breath test (ABT) at any time during the study.
• Subject is not willing to refrain from caffeine/xanthine containing products in the 48 hours prior to admission to the clinical unit on Day -1 and for the duration of the residential period.
• Subject who has a positive human immunodeficiency virus (HIV) screen, Hepatitis B screen or Hepatitis C screen.
• Subject has donated blood or blood products (e.g., plasma or platelets) within the three months prior to screening.
• Subject who is not suitable to participate in the study in the opinion of the Investigator;
• Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing.
• Administrative or legal supervision.
• Subject who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study. -

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

Location

MeSH Terms

Interventions

DF2755A

Limitations and Caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: dr. Mauro P. Ferrari
• Organization: Dompé farmaceutici SpA

clinops@pec.dompe.it

+39 02 583831

Study Officials

• Yves Donazzolo, MD, MSc

  Eurofins Optimed

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is a double blind study. The analytical centre as well as the Investigator and the team and the subjects were in blind conditions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 17, 2021
• Study Start: November 15, 2018
• Primary Completion: June 29, 2019
• Study Completion: June 29, 2019
• Last Updated: April 26, 2024
• Results First Posted: April 26, 2024

Record last verified: 2023-11

Locations

FR (1)