"First-in-human" Study To Assess the Safety and Tolerability of PBF-677 in Healthy Volunteers

NCT02639975 | Completed Phase 1

• 1 other identifier: CUNFI-1509
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

The proposed trial a "Randomized, Double Blind, Placebo Controlled "first in-human" Study to Assess the Safety and Tolerability of Single Ascending Oral Doses of PBF-677 in Male Healthy Volunteers" (Protocol Code No:CUNFI-1509 EudraCT No:2015-003546-57) will be a single-centre, randomized, double-blind, dose escalation study without therapeutic benefit, in which PBF-677 will be administered as single, oral, ascending-dose to volunteers. Up to four different rising doses (100 mg, 200 mg, 400 mg and 600 mg) will be tested in groups of 8 participants; in each dose level participants will be randomized to active drug or placebo in a 6:2 fashion. As this will be the first time that PBF-677 in going to be administered to humans, as a safety measure a stepwise drug administration will be performed in each cohort. The volunteers of each cohort will be divided in 3 blocks/subgroups: Initially, 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 and after further 48h of safety and tolerability assessments a third subgroup of 4 volunteers will receive 3 active drug and 1 placebo. After evaluation of safety, parameters of corresponding dose level the process will replicate one week afterwards in the following dosages. The principal variable safety and tolerability of PBF-677 will be evaluated with physical records (Electrocardiogram (ECG), vital signs, blood chemistry and haematology, conducted before, during and after study course). Assessment of the pharmacokinetic profile (Maximum plasma concentration of the drug (peak) after single dose (Cmax),Time necessary to reach Cmax (tmax), Area under the time-concentration curve to "zero" to time "t" (AUC0t), and Elimination half-life (t1/2) of PBF-677 will be included as secondary variable.

Conditions

Glaucoma

Keywords

Adenosine A3 receptor antagonist

Outcome Measures

Primary Outcomes (1)

• Number of Adverse events

  The occurrence of adverse events will be monitored through the complete study. Adverse events will be recorded with the following information: severity grade (mild, moderate, severe); suspected/unsuspected relationship to the study drug; duration (date and time of onset, defined as precisely as possible, and end date or if continuing at final exam)

  1 week

Secondary Outcomes (8)

• Number of Participants With Abnormal Laboratory Values

  5-7 days post administration

• Electrocardiogram (EKG)

  [pre-dose], [+ 40min], [+ 1.5h], [+ 3h], [+ 24h] and Days (5-7) post-medication

• Vital signs

  [pre-dose], [+ 20 min], [+ 60min], [+ 2h], [+ 4h], [+ 8h], [+ 12h] , [+ 24h] and Days (5-7) post-medication

• Physical examination

  At day-1 (predose), at + 24h post-drug administration and at the follow-up (5-7) days

• Maximum plasma concentration of PBF-677 (peak) after single dose (Cmax)

  0-24 h post dose

Study Arms (8)

100 mg PBF-677

EXPERIMENTAL

Drug: PBF-677

200 mg PBF-677

EXPERIMENTAL

Drug: PBF-677

400 mg PBF-677

EXPERIMENTAL

Drug: PBF-677

600 mg PBF-677

EXPERIMENTAL

Drug: PBF-677

Placebo 100 mg

PLACEBO COMPARATOR

Drug: Placebo

Placebo 200 mg

PLACEBO COMPARATOR

Drug: Placebo

Placebo 400 mg

PLACEBO COMPARATOR

Drug: Placebo

Placebo 600 mg

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PBF-677 DRUG

once daily oral administration

100 mg PBF-677; 200 mg PBF-677; 400 mg PBF-677; 600 mg PBF-677

Placebo DRUG

once daily oral administration

Placebo 100 mg; Placebo 200 mg; Placebo 400 mg; Placebo 600 mg

Eligibility Criteria

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

You may qualify if:

• Healthy male subjects, 18-45 years (inclusive) of age at the time of enrollment.
• Males should agree to abstain from sexual intercourse with a female partner or agree to use a condom with spermicide, in addition to having their female partner use some contraceptive measures as oral contraceptive drugs, intrauterine hormonal contraception, or cervical caps until 28 days post-administration.
• Clinically acceptable blood pressure and pulse rate in supine and standing position (SBP between 140-100 mm Hg/ DBP between 90-50 mm Hg / HR between 100-50 bpm). 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).
• 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 (CEIC).

You may not qualify if:

• 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.
• Smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 6 months prior to the administration of the study medication).
• History of alcohol dependence or drug abuse in the last 5 years or daily consumption of alcohol \> 40 g 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 investigational drug and non prescription medication or herbal medicines within 7 days prior to the administration of the drug. Paracetamol (acetaminophen) is allowed, at doses up to 1 g daily, at the investigator discretion.
• 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 ≥ 440 msec, bradycardia (\<50 bpm) or clinically significant minor ST wave changes or any other abnormal changes on the screening ECG that would interfere with measurement of the QT interval.
• Symptoms of a significant somatic or mental illness in the four week period preceding drug administration.
• History of hepatitis HBV and / or HCV and / or positive serology results which indicate the presence of hepatitis B surface antigen and / or detectable HCV ribonucleic acid (RNA).
• Positive results from the HIV serology.

Sponsors & Collaborators

• Palobiofarma SL: lead

MeSH Terms

Conditions

Glaucoma

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Study Design

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

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 28, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 17, 2018

Record last verified: 2016-09