AsthmaPhase 1NCT01845181
"First-in-human" Study To Assess the Safety and Tolerability of PBF-680 in Male Healthy Volunteers
A Phase 1 study testing PBF-680 in people with Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 2 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- PBF-680
- 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
- 2 sitesSpain
- Study dates
- Apr 2013to Sep 2013
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Each subject must meet all of the following inclusion criteria at the pre-study screening visit (within 4 weeks prior to dosing) in order to participate in this study.
- 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).
Who cannot join
- 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.
Show all 20Show fewer
- 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.
- Having donated blood during 3 month 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 (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.
- Clinically significant abnormal laboratory values (as determined by the Principal Investigator) at the screening evaluation.
- Positive results of the drug screening the day before starting treatment period.
- Known hypersensitivity to the study drug or the composition of the galenical form
- History of psychiatric diseases or epileptic seizures
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
CIM-Sant Pau. Hospital de la Santa Creu i Sant Pau
Barcelona, Catalonia, 08025
Palobiofarma S.L. (molecule owner)
Mataró, Barcelona, 08302
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-680 in Male Healthy Volunteers
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:
Read more
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
Read the detailed description
In order 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.
- Physical Examination. Physical examination data will be collected at screening and at the end of the study. All occurring abnormalities will be displayed by subjects. Vital Signs. Vital signs (DINAMAP V100) including measurements of blood pressure, pulse and respiratory rate and digital axillary temperature will be obtained at screening, during study and at study completion (follow up). All occurring abnormalities will be displayed by subjects.
- Adverse Events. All information obtained on adverse events will be displayed and tallied by treatment /dose. Laboratory variables (Hematology, Biochemistry and Urinalysis): Clinical laboratory data will be collected at screening, during study and at study completion(follow up). All subjects with values outside of the normal range for any variable will be identified. All occurring abnormalities will be displayed by subjects.
- Electrocardiographic Evaluation. An electrocardiogram will be performed at several times, at screening, during the study and at completion of the study (follow up). Description of ECG intervals will be also done. All occurring abnormalities will be identified.
Also, as secondary variables will be evaluated:
- Pharmacokinetic profile analysis. The variable for the pharmacokinetic evaluation will be the parameter that defines the bioavailability in extend and rate Ln [AUC 0t](AUC: area under curve), Ln [Cmax] of experimental products and placebo. For this purpose the necessary kinetic parameters will be determined by means of a non compartmental method with the values obtained after the quantitative analysis of the plasma levels of PBF-680. The following pharmacokinetic parameters will be obtained from each individual plasma concentration versus time profile using standard methods, if the data warrant doing so
- Pharmacodynamic effects. To asses the preliminary pharmacodynamic effects of PBF-680 at each dose level, subjective tests (VAS) and (LSEQ) before and after different times post-drug administration will be conducted. Effects on the CNS (Central Nervous system) will be evaluated by analyzing of the changes observed in the different time for subjective assessment scales.
- Conditions
- Asthma
- Being tested
- PBF-680, Placebo
- Keywords
- Adenosine A1 receptor antagonist, Asthma, adenosine receptor modulator, COPD
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBF-680Drug
Dose: 10, 20, 40 ,60 mg/day (making combination of 5 y 20 mg forms).
PlaceboDrug
1 or 2 or 3 capsules of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level I - Group A - Placebo | Placebo comparator | 2 capsules of placebo Receives: Drug: Placebo |
| Dose Level II - Group B - Active | Experimental | 20 mg: 1 capsule of 20 mg PBF-680 Receives: Drug: PBF-680 |
| Dose Level II - Group B - Placebo | Placebo comparator | 1 capsule of placebo Receives: Drug: Placebo |
| Dose Level I - Group A - Active | Experimental | 10 mg: 2 capsules of 5 mg PBF-680 Receives: Drug: PBF-680 |
| Dose Level III - Group C - Active | Experimental | 40 mg: 2 capsules of 20 mg PBF-680 Receives: Drug: PBF-680 |
| Dose Level III - Group C - Placebo | Placebo comparator | 2 capsules of placebo Receives: Drug: Placebo |
| Dose Level IV - Group D - Active | Experimental | 60 mg: 3 capsules of 20 mg PBF-680 Receives: Drug: PBF-680 |
| Dose Level IV - Group D - Palcebo | Placebo comparator | 3 capsules of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 5-7 days post-dose administration
Secondary outcomes (1)
Pharmacokinetic profile analysis
The main variable for the pharmacokinetic evaluation will be the parameter that defines the bioavailability in extend and rate Ln [AUC 0t], Ln [Cmax] of experimental products and placebo.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startApr 2013
- Primary completionAug 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Palo Biofarma, S.L
- Responsible party
- Sponsor
- Investigators
- Rosa M Antonijoan, MD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01845181
- Sponsor's protocol ID
- IIBSP-PBF-2012-163
- Other IDs
- 2012-005305-44
- Status last verified
- Mar 2016
- First submitted
- 19 Apr 2013
- Last updated
- 8 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2016. 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-680 in Male Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01845181
- Acronym / sponsor ID
- IIBSP-PBF-2012-163
- Conditions
- Asthma
- Keywords
- Adenosine A1 receptor antagonist, Asthma, adenosine receptor modulator, COPD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Collaborators
- Palo Biofarma, S.L
- Study start
- Apr 2013
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 3 May 2013 (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.
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
Detailed description
In order 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.
- Physical Examination. Physical examination data will be collected at screening and at the end of the study. All occurring abnormalities will be displayed by subjects. Vital Signs. Vital signs (DINAMAP V100) including measurements of blood pressure, pulse and respiratory rate and digital axillary temperature will be obtained at screening, during study and at study completion (follow up). All occurring abnormalities will be displayed by subjects.
- Adverse Events. All information obtained on adverse events will be displayed and tallied by treatment /dose. Laboratory variables (Hematology, Biochemistry and Urinalysis): Clinical laboratory data will be collected at screening, during study and at study completion(follow up). All subjects with values outside of the normal range for any variable will be identified. All occurring abnormalities will be displayed by subjects.
- Electrocardiographic Evaluation. An electrocardiogram will be performed at several times, at screening, during the study and at completion of the study (follow up). Description of ECG intervals will be also done. All occurring abnormalities will be identified.
Also, as secondary variables will be evaluated:
- Pharmacokinetic profile analysis. The variable for the pharmacokinetic evaluation will be the parameter that defines the bioavailability in extend and rate Ln [AUC 0t](AUC: area under curve), Ln [Cmax] of experimental products and placebo. For this purpose the necessary kinetic parameters will be determined by means of a non compartmental method with the values obtained after the quantitative analysis of the plasma levels of PBF-680. The following pharmacokinetic parameters will be obtained from each individual plasma concentration versus time profile using standard methods, if the data warrant doing so
- Pharmacodynamic effects. To asses the preliminary pharmacodynamic effects of PBF-680 at each dose level, subjective tests (VAS) and (LSEQ) before and after different times post-drug administration will be conducted. Effects on the CNS (Central Nervous system) will be evaluated by analyzing of the changes observed in the different time for subjective assessment scales.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Dose Level I - Group A - Placebo | Placebo comparator | Drug: Placebo2 capsules of placebo |
| Dose Level II - Group B - Active | Experimental | Drug: PBF-68020 mg: 1 capsule of 20 mg PBF-680 |
| Dose Level II - Group B - Placebo | Placebo comparator | Drug: Placebo1 capsule of placebo |
| Dose Level I - Group A - Active | Experimental | Drug: PBF-68010 mg: 2 capsules of 5 mg PBF-680 |
| Dose Level III - Group C - Active | Experimental | Drug: PBF-68040 mg: 2 capsules of 20 mg PBF-680 |
| Dose Level III - Group C - Placebo | Placebo comparator | Drug: Placebo2 capsules of placebo |
| Dose Level IV - Group D - Active | Experimental | Drug: PBF-68060 mg: 3 capsules of 20 mg PBF-680 |
| Dose Level IV - Group D - Palcebo | Placebo comparator | Drug: Placebo3 capsules of placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Each subject must meet all of the following inclusion criteria at the pre-study screening visit (within 4 weeks prior to dosing) in order to participate in this study.
- 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).
Key exclusion criteria (20 listed)
- 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.
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-680Dose: 10, 20, 40 ,60 mg/day (making combination of 5 y 20 mg forms). | Drug | Dose Level I - Group A - Active, Dose Level II - Group B - Active, Dose Level III - Group C - Active, Dose Level IV - Group D - Active |
| Placebo1 or 2 or 3 capsules of placebo. | Drug | Dose Level I - Group A - Placebo, Dose Level II - Group B - Placebo, Dose Level III - Group C - Placebo, Dose Level IV - Group D - Palcebo |
Primary outcome
Number of Adverse Events
Time frame: up to 5-7 days post-dose administration
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.
1 secondary outcome
Pharmacokinetic profile analysis
Time frame: 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.
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 8 Mar 2016.
Related trials for Asthma
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
RecruitingObservational study
Construction and Validation of an Impulse Oscillometry (IOS)-Based Platform for Screening, Diagnosis, and Management of Chronic Airway Diseases
Chronic Obstructive Pulmonary Disease (COPD), Asthma (Diagnosis)
RecruitingObservational study
Swiss Severe Asthma Register
Severe Asthma
RecruitingPhase 3
A Study to Learn About the Study Medicine Called Tilrekimig in People With Severe Asthma
Asthma
RecruitingPhase 2
Dose Range Finding Study to Assess Efficacy and Safety of Tozorakimab in Adults With Uncontrolled Asthma on Medium-to-High Dose Inhaled Corticosteroids
Asthma
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.
Rosa M Antonijoan, MD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBF-680 in people with Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 2 sites in Spain.
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 7 inclusion and 20 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 8 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
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: up to 5-7 days post-dose administration). 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 8 Mar 2016.