GlaucomaPhase 1NCT02639975
"First-in-human" Study To Assess the Safety and Tolerability of PBF-677 in Healthy Volunteers
A Phase 1 study testing PBF-677 in people with Glaucoma, run by Palobiofarma SL.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Glaucoma
- What is being tested?
- PBF-677
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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).
Show all 21Show fewer
- 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.
- Having donated blood during 3 months period before inclusion in the study.
- 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
- 12 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.
- Clinically significant abnormal laboratory values (as determined by the Principal Investigator) at the screening evaluation.
- Positive results of the drugs at screening period or the day before starting treatment period. A minimum list of 6 drugs will be screened for inclusion: Amphetamines, Cocaine, Ethanol, Opiates, Cannabinoids and Benzodiazepines (positive results may be repeated at the discretion of the Principal Investigator).
- Known hypersensitivity to the study drug or the composition of the galenical form.
- History of psychiatric diseases or epileptic seizures.
- Pill swallowing difficulties.
About this study
Official title: Randomized, Double Blind, Placebo Controlled "First-in-human" Study To Assess the Safety and Tolerability of Single Ascending Oral Doses of PBF-677 ( 100 mg, 200 mg, 400 mg and 600 mg ) in Healthy Young Male Volunteers
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
- Being tested
- PBF-677, Placebo
- Keywords
- Adenosine A3 receptor antagonist
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBF-677Drug
once daily oral administration
PlaceboDrug
once daily oral administration
| Study group | Role | What they receive |
|---|---|---|
| 100 mg PBF-677 | Experimental | Not described Receives: Drug: PBF-677 |
| 200 mg PBF-677 | Experimental | Not described Receives: Drug: PBF-677 |
| 400 mg PBF-677 | Experimental | Not described Receives: Drug: PBF-677 |
| 600 mg PBF-677 | Experimental | Not described Receives: Drug: PBF-677 |
| Placebo 100 mg | Placebo comparator | Not described Receives: Drug: Placebo |
| Placebo 200 mg | Placebo comparator | Not described Receives: Drug: Placebo |
| Placebo 400 mg | Placebo comparator | Not described Receives: Drug: Placebo |
| Placebo 600 mg | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 1 week
Secondary outcomes (8)
Number of Participants With Abnormal Laboratory Values
The following laboratory evaluations will be performed at the study site:
- Hematology - Hemoglobin, Hematocrit, White Blood Cells (WBC) with differential, Red Blood Cells (RBC) count, Platelet count.
- Biochemistry - Sodium, Potassium, Calcium, Inorganic Phosphorus, Total Proteins, Total Bilirubin, Albumin, Fasting Cholesterol, Fasting Triglycerides, Serum Creatinine, Creatine Kinase (CK), Fasting Glucose, Aspartate amino transferase (AST), Alanine amino transferase (ALT), Glutamyl transpeptidase (GGT), Alkaline Phosphatase, BUN (urea-N), Uric Acid.
- Urinalysis - Glucose, Leukocytes, Ketonic Bodies, Nitrites, Proteins, Bilirubin, Urobilinogen and Erythrocytes. A midstream urine sample will be obtained, in order to avoid contamination and allow a proper assessment.
Measured: 5-7 days post administration
Electrocardiogram (EKG)
Measured: [pre-dose], [+ 40min], [+ 1.5h], [+ 3h], [+ 24h] and Days (5-7) post-medication
Vital signs
This evaluation will include automated/manual assessments of systolic and diastolic blood pressure, heart and respiratory rate.
Measured: [pre-dose], [+ 20 min], [+ 60min], [+ 2h], [+ 4h], [+ 8h], [+ 12h] , [+ 24h] and Days (5-7) post-medication
Physical examination
This evaluation will include an examination of general appearance, eyes, throat-nose-ears, teeth, skin, lung, heart, abdomen general, liver, spleen, kidneys, spine, lymph nodes, extremities, short neurological status. Genital, urinary tract and rectal examination will not be done on a routine basis.
Measured: 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)
The Blood extractions will be done at the following time points: Baseline [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-medication. Plasma concentrations of parent compound (PBF-677) will be measured with a previously validated method. The Pharmacokinetic (PK) parameter will be derived from each individual plasma concentration versus time profile using standard methods.
Measured: 0-24 h post dose
Time necessary to reach Maximum plasma concentration of PBF-677 (Tmax)
The Blood extractions will be done at the following time points: Baseline [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-medication. Plasma concentrations of parent compound (PBF-677) will be measured with a previously validated method. The Pharmacokinetic (PK) parameter will be derived from each individual plasma concentration versus time profile using standard methods.
Measured: 0-24 h post dose
Area under the time-concentration curve to "zero" to time "t" (AUC0t)
The Blood extractions will be done at the following time points: Baseline [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-medication. Plasma concentrations of parent compound (PBF-677) will be measured with a previously validated method. The Pharmacokinetic (PK) parameter will be derived from each individual plasma concentration versus time profile using standard methods.
Measured: 0-24 h post dose
Elimination half-life (t1/2) of PBF-677
The Blood extractions will be done at the following time points: Baseline [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-medication. Plasma concentrations of parent compound (PBF-677) will be measured with a previously validated method. The Pharmacokinetic (PK) parameter will be derived from each individual plasma concentration versus time profile using standard methods.
Measured: 0-24 h post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionApr 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Palobiofarma SL
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02639975
- Sponsor's protocol ID
- CUNFI-1509
- Status last verified
- Sep 2016
- First submitted
- 17 Dec 2015
- Last updated
- 17 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind, Placebo Controlled "First-in-human" Study To Assess the Safety and Tolerability of Single Ascending Oral Doses of PBF-677 ( 100 mg, 200 mg, 400 mg and 600 mg ) in Healthy Young Male Volunteers
- ClinicalTrials.gov ID
- NCT02639975
- Acronym / sponsor ID
- CUNFI-1509
- Conditions
- Glaucoma
- Keywords
- Adenosine A3 receptor antagonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Palobiofarma SLIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 28 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PBF-677once daily oral administration | Drug | 100 mg PBF-677, 200 mg PBF-677, 400 mg PBF-677, 600 mg PBF-677 |
| Placeboonce daily oral administration | Drug | Placebo 100 mg, Placebo 200 mg, Placebo 400 mg, Placebo 600 mg |
Primary outcome
Number of Adverse events
Time frame: 1 week
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)
8 secondary outcomes
Number of Participants With Abnormal Laboratory Values
Time frame: 5-7 days post administration
Electrocardiogram (EKG)
Time frame: [pre-dose], [+ 40min], [+ 1.5h], [+ 3h], [+ 24h] and Days (5-7) post-medication
Vital signs
Time frame: [pre-dose], [+ 20 min], [+ 60min], [+ 2h], [+ 4h], [+ 8h], [+ 12h] , [+ 24h] and Days (5-7) post-medication
Physical examination
Time frame: 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)
Time frame: 0-24 h post dose
Time necessary to reach Maximum plasma concentration of PBF-677 (Tmax)
Time frame: 0-24 h post dose
Area under the time-concentration curve to "zero" to time "t" (AUC0t)
Time frame: 0-24 h post dose
Elimination half-life (t1/2) of PBF-677
Time frame: 0-24 h post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBF-677 in people with Glaucoma, run by Palobiofarma SL.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse events (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2018.