"First-in-human" Study To Assess the Safety and Tolerability of PBF-680 in Male Healthy Volunteers

NCT01845181 | Completed Phase 1 DMC

• 2 other identifiers: IIBSP-PBF-2012-1632012-005305-44
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I, single-center, randomized, double-blind, dose escalation study without therapeutic benefit, in which PBF-680 will be administered as single oral ascending dose to young male healthy volunteers. Up to four different rising doses will be tested in groups of 8 participants. Thus, four groups will participate but each one participating only once. For each dose level / group the participants will be randomized to active or placebo with 2 participants being randomly assigned to placebo and 6 to the active drug. First, one volunteer will receive active drug (subgroup 1); after 48h of safety and tolerability assessment a second subgroup of 3 volunteers will receive 2 active drug and 1 placebo; after 48h of safety and tolerability parameters assessment a third subgroup of 4 volunteers will receive 3 active drug and 1 placebo. After evaluation of safety parameters of dose level the process will replicate one week afterwards in the following dosages. The aims of this study are: Primary: \- To assess the safety and tolerability of single escalating oral doses of PBF-680 in young male healthy subjects leading to the determination of the maximum tolerated dose (MTD). Secondary:

• To assess the pharmacokinetics of PBF-680 after single rising oral doses in healthy young male subjects.
• To asses the preliminary pharmacodynamic effects.
• To evaluate the adenosine A1 receptor antagonism in blood samples of healthy volunteer caused by the PBF-680 administration

Conditions

Asthma

Keywords

Adenosine A1 receptor antagonist; Asthma; adenosine receptor modulator; COPD

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  Safety and Tolerability evaluation To assess the safety and tolerability of single escalating oral doses of PBF-680, safe measurements: ECG, vital signs, blood chemistry and hematology, will be conducted before, during and follow-up study course.

  up to 5-7 days post-dose administration

Secondary Outcomes (1)

• Pharmacokinetic profile analysis

  pre-dose; +10 min, + 20 min; + 40 min; + 60 min; + 1.5h; + 2 h; + 2.5 h; + 3 h; + 4h; + 8h; + 12h; + 16h; and + 24h post-dose administration and after recording vital signs.

Study Arms (8)

Dose Level I - Group A - Placebo

PLACEBO COMPARATOR

2 capsules of placebo

Drug: Placebo

Dose Level II - Group B - Active

EXPERIMENTAL

20 mg: 1 capsule of 20 mg PBF-680

Drug: PBF-680

Dose Level II - Group B - Placebo

PLACEBO COMPARATOR

1 capsule of placebo

Drug: Placebo

Dose Level I - Group A - Active

EXPERIMENTAL

10 mg: 2 capsules of 5 mg PBF-680

Drug: PBF-680

Dose Level III - Group C - Active

EXPERIMENTAL

40 mg: 2 capsules of 20 mg PBF-680

Drug: PBF-680

Dose Level III - Group C - Placebo

PLACEBO COMPARATOR

2 capsules of placebo

Drug: Placebo

Dose Level IV - Group D - Active

EXPERIMENTAL

60 mg: 3 capsules of 20 mg PBF-680

Drug: PBF-680

Dose Level IV - Group D - Palcebo

PLACEBO COMPARATOR

3 capsules of placebo

Drug: Placebo

Interventions

PBF-680 DRUG

Dose: 10, 20, 40 ,60 mg/day (making combination of 5 y 20 mg forms).

Dose Level I - Group A - Active; Dose Level II - Group B - Active; Dose Level III - Group C - Active; Dose Level IV - Group D - Active

Placebo DRUG

1 or 2 or 3 capsules of placebo.

Dose Level I - Group A - Placebo; Dose Level II - Group B - Placebo; Dose Level III - Group C - Placebo; Dose Level IV - Group D - Palcebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects, 18-45 years of age.
• Clinically acceptable blood pressure and pulse rate in supine and standing position. Blood pressure and pulse will be measured after a minimum of 3 minutes of resting.
• Body weight within normal range (Quetelet's index between 19 and 26) expressed as weight (kg) / height (m2).
• Non-smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 6 months prior to the administration of the study medication).
• Able to understand the nature of the study and comply with all their requirements.
• Free acceptance to participate in the study by obtains signed informed consent form approved by the Ethics Committee of the Hospital (CEIC).

You may not qualify if:

• Subjects meeting any of the following criteria at screening will be excluded from entry into the study:
• History of serious adverse reactions or hypersensitivity to any drug.
• Presence or history of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis).
• Background or clinical evidence of chronic diseases.
• Acute illness two weeks before drug administration.
• Having undergone major surgery during the previous 6 months.
• History of alcohol or drug abuse in the last 5 years or daily consumption of alcohol \> 40 g for men or high consumption of stimulating beverages (\> 5 coffees, teas or coca cola drinks/ day)
• Abnormal physical findings of clinical significance at the screening examination or baseline which would interfere with the objectives of the study.
• Need of any prescription medication within 14 days prior to the administration of the drug and non prescription medication or herbal medicines within 7 days prior to the administration of the drug.
• Participation in other clinical trials during the previous 90 days in which an investigational drug or a commercially available drug was tested.
• Existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the drug, i.e. impaired renal or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic symptoms of pronounced constipation or diarrhea or conditions associated with total or partial obstruction of the urinary tract.
• lead ECG obtained at screening with PR ≥ 220 msec, QRS ≥120 msec and QTc (corrected QT interval) ≥ 440 msec, bradycardia (\<50 bpm) or clinically significant minor ST wave changes or any other abnormal changes on the screening ECG.
• Symptoms of a significant somatic or mental illness in the four week period preceding drug administration.
• History of hepatitis B and / or C and / or positive serology results which indicate the presence of hepatitis B and / or C.
• Positive results from the HIV serology.

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead
• Palo Biofarma, S.L: collaborator

Study Sites (2)

Palobiofarma S.L. (molecule owner)

Mataró, Barcelona, 08302, Spain

Location

CIM-Sant Pau. Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08025, Spain

Location

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rosa M Antonijoan, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2013
• First Posted: May 3, 2013
• Study Start: April 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 8, 2016

Record last verified: 2016-03

Locations

ES (2)