Acute PainPhase 1NCT02982889
Single Ascending Dose Study of Two Liquidia Bupivacaine Formulations
A Phase 1 study testing LIQ865A bupivacaine formulation, LIQ865B bupivacaine formulation and Diluent for LIQ865 in people with Acute Pain, run by Liquidia Technologies, Inc. at 1 site in Denmark.
Trial summary
This study is designed to assess and characterize the safety and tolerability profile of LIQ865A and LIQ865B formulations compared to diluent or aqueous bupivacaine hydrochloride when infiltrated into a defined area of the medial calf, and to characterize bupivacaine plasma pharmacokinetic (PK) and pharmacodynamic… 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
- Acute Pain
- What is being tested?
- LIQ865A bupivacaine formulation, LIQ865B bupivacaine formulation and Diluent for LIQ865
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Dec 2016to 26 Apr 2017
- 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
- provide written informed consent prior to enrollment
- be a non-smoking male, American Society of Anesthesiologist (ASA) physical class 1 or 2
- have a BMI between 18.5 and 25 kg. inclusive, and a weight of at least 60 kg
- be willing and able to participate for the duration of the study
- be healthy on the basis of pre-study physical examination (PE), medical history review, vital signs, lab test results as specified in the protocol
- negative urine drug test results
- negative alcohol screening test
- negative antibody test results for hepatitis B, hepatitis C, and HIV
Who cannot join
- allergic to bupivacaine, or other amide local anesthetics, or the excipients in the LIQ865 formulations or the diluent
- has taken any concomitant medications or supplements for the 3 days prior to Day 0
- has been on blood thinner or medication affecting platelet formation for the 7 days prior to Day 0
- in the opinion of the investigator, is either a hyper or hypo-responder to screening sensitivity testing
- has a history of moderate or severe renal or hepatic impairment, moderate or severe active hepatic disease, or any other clinically significant medical condition that may preclude safe study participation
- has a clinically significant test result for any screening lab parameter
Show all 11Show fewer
- has a history or ECG screening documentation of a clinically meaningful conduction abnormality
- has scarring, tattoos, infections, or other skin changes in the area of planned study medication injection
- has known neurological disease or dysfunction (central or peripheral) that may interfere with assessments
- is unable to adequately communicate with study staff, properly give informed consent, or otherwise comply with study procedures, particularly the ability to return for outpatient follow up visits
- has participated in another interventional clinical study (investigational or marketed product) within the 30 days prior to Day 0.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Randomized, Controlled, Double-Blind, Single Ascending Dose Safety and Pharmacokinetic/Pharmacodynamic Study in Healthy Adult Males After LIQ865 Injection
This study is designed to assess and characterize the safety and tolerability profile of LIQ865A and LIQ865B formulations compared to diluent or aqueous bupivacaine hydrochloride when infiltrated into a defined area of the medial calf, and to characterize bupivacaine plasma pharmacokinetic (PK) and pharmacodynamic (PD) profiles after a single dose of LIQ865A or LIQ865B, and to determine the individual plasma concentration/time curves and mean PK parameters of each product.
Read the detailed description
Infiltration of an aqueous local anesthetic, for example, bupivacaine, into surgical sites at closure provides temporary analgesia, typically lasting up to 6 hours, and is one aspect of the multimodal approach to postsurgical analgesia or fast-track surgery. However, the limited duration of action of local anesthetics, even longer acting agents such as bupivacaine, result in patients who are likely to experience end of duration breakthrough pain before they are able to take or tolerate oral analgesics, thus necessitating the use of strong parenteral analgesics in the immediate postsurgical period. LIQ865A and LIQ865B are two distinct formulations of bupivacaine manufactured via Liquidia Technologies PRINT (Particle Replication In Non-wetting Templates), which Liquidia intends to pursue for product approval. Both formulations being tested have the potential for producing long-lasting control of post-surgical incisional pain.
- Conditions
- Acute Pain
- Being tested
- LIQ865A bupivacaine formulation, LIQ865B bupivacaine formulation, Diluent for LIQ865, 0.5% bupivacaine hydrochoride
- Keywords
- Analytical, Diagnostic,Therapeutic Technique and Equipment, Anesthesia and Analgesia
- Medical subject headings
- Acute Pain, Disease, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LIQ865A bupivacaine formulationDrug
Also called Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF
single subcutaneous injection in medial calf
LIQ865B bupivacaine formulationDrug
Also called Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF
single subcutaneous injection in medial calf
Diluent for LIQ865Drug
Also called Hyaluronic Acid
Sterile diluent composed of 12.5mg/g sodium hyaluronate, 5.8mg/g sodium chloride, 1mg/g polysorbate 80, 6.1mg/g Tris base, in sterile water for injection - single subcutaneous injection
0.5% bupivacaine hydrochorideDrug
Also called Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF
single subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| LIQ865A bupivacaine formulation | Experimental | Liquidia's PRINT bupivacaine free base/PLGA (poly D,L-lactic-co-glycolic acid) suspension for subcutaneous injection at doses ranging from 150mg to 600mg Receives: Drug: LIQ865A bupivacaine formulation; Drug: Diluent for LIQ865 |
| LIQ865B bupivacaine formulation | Experimental | Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg Receives: Drug: LIQ865B bupivacaine formulation; Drug: Diluent for LIQ865 |
| Diluent for LIQ865 | Placebo comparator | Negative control for subcutaneous injection. Each subject will act as his own control, receiving a LIQ865 formulation subcutaneous injection in one calf, and a diluent subcutaneous injection in his other calf Receives: Drug: LIQ865A bupivacaine formulation; Drug: LIQ865B bupivacaine formulation; Drug: Diluent for LIQ865 |
| 0.5% bupivacaine hydrochoride | Active comparator | Positive control arm to be used with one of the LIQ865 cohorts, with each subject acting as his own positive control (i.e., one leg will receive subcutaneous injection of LIQ865A or LIQ865B, and the other leg will receive subcutaneous injection of 0.5% bupivacaine hydrochloride). Receives: Drug: LIQ865A bupivacaine formulation; Drug: LIQ865B bupivacaine formulation; Drug: 0.5% bupivacaine hydrochoride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment Emergent Adverse Events (AEs)
Safety assessments will include the incidence and severity of AEs during treatment and the follow-up period of the study
Measured: 30 days
Secondary outcomes (11)
Pharmacokinetic - Area under the plasma concentration curve from time zero to Day 5
Measured: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Cmax (ng/mL)
Maximum plasma concentration over the entire sampling period, directly obtained from the experimental data of plasma concentration versus time curves, without interpolation.
Measured: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Tmax (h)
Time to reach maximum plasma concentration
Measured: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - t1/2 (h)
Apparent terminal elimination half-life
Measured: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - CST1/2 (h)
Context-sensitive half-time measured from Tmax to time for plasma concentration to reach half of Cmax following study medication injection.
Measured: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacodynamic Response - Pain intensity (Numeric Rating Scale) with Short Tonic Heat Stimulus (STHS) testing at various time points
Testing done to calculate time-weighted Sum of Pain Intensity Differences (SPID) at the time points noted, compared to Baseline, and time specific SPID results
Measured: 1, 2, 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Mechanical Pain Threshold (MPT) compared to Baseline using various time points
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
Measured: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Heat Pain Threshold (HPT) compared to Baseline using various time points
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
Measured: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change Mechanical Detection Threshold (MDT) compared to Baseline using various time points
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
Measured: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Warmth Detection Threshold (WDT) compared to Baseline using various time points
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
Measured: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Cold Detection Threshold (CDT) compared to Baseline using various time points
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
Measured: 12, 24, 48, 72, 96, and 120 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study start5 Dec 2016
- Primary completion23 Mar 2017
- Study completion26 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute PainStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liquidia Technologies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Responsible party
- Sponsor
- Investigators
- Mads U Werner, MD, Principal investigator, Multidisciplinary Pain Center, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02982889
- Sponsor's protocol ID
- LTI-111
- Other IDs
- 2016-002420-88, 2016
- Status last verified
- Aug 2017
- First submitted
- 22 Nov 2016
- Last updated
- 24 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, Controlled, Double-Blind, Single Ascending Dose Safety and Pharmacokinetic/Pharmacodynamic Study in Healthy Adult Males After LIQ865 Injection
- ClinicalTrials.gov ID
- NCT02982889
- Acronym / sponsor ID
- LTI-111
- Conditions
- Acute Pain
- Keywords
- Analytical, Diagnostic,Therapeutic Technique and Equipment, Anesthesia and Analgesia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Liquidia Technologies, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Study start
- 5 Dec 2016 (actual)
- Primary completion
- 23 Mar 2017 (actual)
- Study completion
- 26 Apr 2017 (actual)
- First posted
- 6 Dec 2016 (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 study is designed to assess and characterize the safety and tolerability profile of LIQ865A and LIQ865B formulations compared to diluent or aqueous bupivacaine hydrochloride when infiltrated into a defined area of the medial calf, and to characterize bupivacaine plasma pharmacokinetic (PK) and pharmacodynamic (PD) profiles after a single dose of LIQ865A or LIQ865B, and to determine the individual plasma concentration/time curves and mean PK parameters of each product.
Detailed description
Infiltration of an aqueous local anesthetic, for example, bupivacaine, into surgical sites at closure provides temporary analgesia, typically lasting up to 6 hours, and is one aspect of the multimodal approach to postsurgical analgesia or fast-track surgery. However, the limited duration of action of local anesthetics, even longer acting agents such as bupivacaine, result in patients who are likely to experience end of duration breakthrough pain before they are able to take or tolerate oral analgesics, thus necessitating the use of strong parenteral analgesics in the immediate postsurgical period. LIQ865A and LIQ865B are two distinct formulations of bupivacaine manufactured via Liquidia Technologies PRINT (Particle Replication In Non-wetting Templates), which Liquidia intends to pursue for product approval. Both formulations being tested have the potential for producing long-lasting control of post-surgical incisional pain.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LIQ865A bupivacaine formulation | Experimental | Drug: LIQ865A bupivacaine formulation, Drug: Diluent for LIQ865Liquidia's PRINT bupivacaine free base/PLGA (poly D,L-lactic-co-glycolic acid) suspension for subcutaneous injection at doses ranging from 150mg to 600mg |
| LIQ865B bupivacaine formulation | Experimental | Drug: LIQ865B bupivacaine formulation, Drug: Diluent for LIQ865Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg |
| Diluent for LIQ865 | Placebo comparator | Drug: LIQ865A bupivacaine formulation, Drug: LIQ865B bupivacaine formulation, Drug: Diluent for LIQ865Negative control for subcutaneous injection. Each subject will act as his own control, receiving a LIQ865 formulation subcutaneous injection in one calf, and a diluent subcutaneous injection in his other calf |
| 0.5% bupivacaine hydrochoride | Active comparator | Drug: LIQ865A bupivacaine formulation, Drug: LIQ865B bupivacaine formulation, Drug: 0.5% bupivacaine hydrochoridePositive control arm to be used with one of the LIQ865 cohorts, with each subject acting as his own positive control (i.e., one leg will receive subcutaneous injection of LIQ865A or LIQ865B, and the other leg will receive subcutaneous injection of 0.5% bupivacaine hydrochloride). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- provide written informed consent prior to enrollment
- be a non-smoking male, American Society of Anesthesiologist (ASA) physical class 1 or 2
- have a BMI between 18.5 and 25 kg. inclusive, and a weight of at least 60 kg
- be willing and able to participate for the duration of the study
- be healthy on the basis of pre-study physical examination (PE), medical history review, vital signs, lab test results as specified in the protocol
Key exclusion criteria (11 listed)
- allergic to bupivacaine, or other amide local anesthetics, or the excipients in the LIQ865 formulations or the diluent
- has taken any concomitant medications or supplements for the 3 days prior to Day 0
- has been on blood thinner or medication affecting platelet formation for the 7 days prior to Day 0
- in the opinion of the investigator, is either a hyper or hypo-responder to screening sensitivity testing
- has a history of moderate or severe renal or hepatic impairment, moderate or severe active hepatic disease, or any other clinically significant medical condition that may preclude safe study participation
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 |
|---|---|---|
| LIQ865A bupivacaine formulationAlso: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPFsingle subcutaneous injection in medial calf | Drug | 0.5% bupivacaine hydrochoride, Diluent for LIQ865, LIQ865A bupivacaine formulation |
| LIQ865B bupivacaine formulationAlso: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPFsingle subcutaneous injection in medial calf | Drug | 0.5% bupivacaine hydrochoride, Diluent for LIQ865, LIQ865B bupivacaine formulation |
| Diluent for LIQ865Also: Hyaluronic AcidSterile diluent composed of 12.5mg/g sodium hyaluronate, 5.8mg/g sodium chloride, 1mg/g polysorbate 80, 6.1mg/g Tris base, in sterile water for injection - single subcutaneous injection | Drug | Diluent for LIQ865, LIQ865A bupivacaine formulation, LIQ865B bupivacaine formulation |
| 0.5% bupivacaine hydrochorideAlso: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPFsingle subcutaneous injection | Drug | 0.5% bupivacaine hydrochoride |
Primary outcome
Incidence of Treatment Emergent Adverse Events (AEs)
Time frame: 30 days
Safety assessments will include the incidence and severity of AEs during treatment and the follow-up period of the study
11 secondary outcomes
Pharmacokinetic - Area under the plasma concentration curve from time zero to Day 5
Time frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Cmax (ng/mL)
Time frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Tmax (h)
Time frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - t1/2 (h)
Time frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - CST1/2 (h)
Time frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacodynamic Response - Pain intensity (Numeric Rating Scale) with Short Tonic Heat Stimulus (STHS) testing at various time points
Time frame: 1, 2, 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Mechanical Pain Threshold (MPT) compared to Baseline using various time points
Time frame: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Heat Pain Threshold (HPT) compared to Baseline using various time points
Time frame: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change Mechanical Detection Threshold (MDT) compared to Baseline using various time points
Time frame: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Warmth Detection Threshold (WDT) compared to Baseline using various time points
Time frame: 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Cold Detection Threshold (CDT) compared to Baseline using various time points
Time frame: 12, 24, 48, 72, 96, and 120 hours
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 24 Aug 2017.
- Individual participant dataSharing planned: No
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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.
Mads U Werner, MD principal investigator
Multidisciplinary Pain Center, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LIQ865A bupivacaine formulation, LIQ865B bupivacaine formulation and Diluent for LIQ865 in people with Acute Pain, run by Liquidia Technologies, Inc. at 1 site in Denmark.
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 8 inclusion and 11 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 24 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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?
Incidence of Treatment Emergent Adverse Events (AEs) (time frame: 30 days). 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 24 Aug 2017.