Back to resultsA Phase 1 Study to Evaluate Pregabalin and Acetaminophen in Healthy Volunteers
Primary Purpose
Postoperative Pain
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pregabalin 100mg
Acetaminophen 1300mg
Sponsored by
About this trial
This is an interventional treatment trial for Postoperative Pain
Eligibility Criteria
Inclusion Criteria:
- Male or female aged 18 to 55 years, inclusive at time of Screening
- Body mass index (BMI) between 18.5 and 28.0 kg/m2 inclusive, with a minimum weight of 50 kg and a maximum of 100 kg
- Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination, and 12-lead ECG confirming normal sinus rhythm
- Negative tests for Hepatitis B surface antigen (HbsAg), hepatitis C virus antibody (anti-HCV), human immunodeficiency virus (HIV)-1 and HIV-2 antibody at Screening
- Routine clinical laboratory tests should be within normal limits at Screening and Admission (Day -1) or abnormalities deemed not clinically significant by the Investigator; for liver function tests, AST and ALT values should not be greater than 1.5 times the upper limit of normal range
- Negative screen for drugs of abuse or exhibit detectable alcohol levels by breathalyzer at the time of Screening or Admission
- Non-smokers or ex-smokers (must have ceased smoking ≥3 months prior Screening visit)
Female subjects:
- Must be of non-childbearing potential by surgical sterilization or postmenopausal OR Must not be pregnant, breast feeding, or planning to become pregnant AND must be practicing both a highly effective method of birth control from Screening until at least 90 days after the last dose of study drug.
- Women of childbearing potential must have a negative pregnancy test result at Screening and upon admission to the Clinical Trial Unit.
Exclusion Criteria:
- Has a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders
- Has a history of severe drug allergy, or severe hypersensitivity or severe food allergy, including anaphylaxis or known allergy or sensitivity to any component of PGB or APAP
- Has a history of alcoholism or drug abuse
- Has acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) at the time of Screening or Admission
- Consumption of drugs with enzyme-inducing properties, within 3 weeks prior to the initial dose of study drug and throughout the treatment phase
- Has used any prescription medicines, over the counter medicines, or herbal supplements, within 7 days of dosing
- Has used any investigational product or participated in any clinical trial within 30 days prior to Screening
- Has donated or received any blood or blood products within the 3 months prior to Screening;
- Not able to comply with the requirements of this study, including assessments, duration of admission of the study and expected follow up visits
- Is unwilling or unable to give written informed consent
Sites / Locations
- Lotus Clinical Resarch,LLC
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
No Intervention
Experimental
Arm Label
1300 mg Acetaminophen and 100 mg IV Pregabalin
Placebo
1300 mg Acetaminophen and 100 mg +/- 25 IV Pregabalin
Arm Description
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg based on Safety Monitoring Committee decision).
Saline solution
Decisions to escalate or decrease the dose for Cohorts 2 through 6 will be dependent upon blinded review of emerging safety and tolerability data by the Safety Monitoring Committee (SMC). However, PK data is not part of the SMC review, but may be reviewed by a SMC designee at a later time.
Outcomes
Primary Outcome Measures
Treatment Related Adverse Events
The incidence and severity of treatment-emergent adverse events
Treatment related Drowsiness and Dizziness
The incidence and severity of somnolence and dizziness
Secondary Outcome Measures
Plasma PK endpoints for APAP and PGB, SAD Phase, Cmax
Maximum observed concentration
Plasma PK endpoints for APAP and PGB, SAD Phase, Tmax
Time to maximum observed drug concentration (Tmax)
Plasma PK endpoints for APAP and PGB, SAD Phase, t1/2
Apparent elimination half-life
Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-last
Area under the drug concentration-time curve from time zero to the last measurable concentration
Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-inf
AUC from time zero to infinity
Plasma PK endpoints for APAP and PGB, SAD Phase, λz
Apparent terminal elimination rate constant
Plasma PK endpoints for APAP and PGB, SAD Phase, CL
Apparent clearance
Plasma PK endpoints for APAP and PGB, SAD Phase, Vz
Apparent terminal volume of distribution
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, AUCτ
Area under the plasma concentration-time curve during a dosage interval
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Tmax,ss
Time to Cmax at SS
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmax,ss
Maximum concentration at SS
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmin,ss
Minimum concentration at ss
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cav,ss
Average plasma concentration at SS
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Vz, ss
Apparent volume of distribution at SS
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, CLss
Apparent total clearance at SS
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, λz,ss
Apparent first order terminal elimination rate constant at steady state
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, R
Accumulation index
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, LF
Linearity factor
Plasma PK endpoints for APAP and PGB, multiple doses at steady state
Fluctuation ratio
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04265456
Brief Title
A Phase 1 Study to Evaluate Pregabalin and Acetaminophen in Healthy Volunteers
Official Title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Pregabalin and Acetaminophen (Ofirmev®) in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
January 14, 2020 (Actual)
Primary Completion Date
June 15, 2020 (Actual)
Study Completion Date
July 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nevakar, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study to determine a maximum tolerated dose of IV PGB and to evaluate the safety, tolerability, and PK of an admixture of IV PGB and a fixed dose of 1300 mg IV APAP in healthy adult volunteers.
Detailed Description
This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study to determine a maximum tolerated dose (MTD) of IV PGB and to evaluate the safety, tolerability, and PK of an admixture of IV PGB and a fixed dose of 1300 mg IV APAP in healthy adult volunteers.
Up to 60 subjects will be enrolled into one (1) of six (6) sequential cohorts (n=10 per cohort [8 APAP + PGB and 2 placebo]).
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg) based on Safety Monitoring Committee decision.
The placebo will be the saline solution.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Up to 60 healthy male and female volunteers will be enrolled into one (1) of up to six (6) cohorts (n=10 per cohort).
Within each cohort, subjects will be randomized at a ratio of 4:1 to receive IP (1300 mg of IV APAP plus a cohort specific dose of IV PGB) or placebo (saline) (8 active:2 placebo).
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1300 mg Acetaminophen and 100 mg IV Pregabalin
Arm Type
Experimental
Arm Description
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg based on Safety Monitoring Committee decision).
Arm Title
Placebo
Arm Type
No Intervention
Arm Description
Saline solution
Arm Title
1300 mg Acetaminophen and 100 mg +/- 25 IV Pregabalin
Arm Type
Experimental
Arm Description
Decisions to escalate or decrease the dose for Cohorts 2 through 6 will be dependent upon blinded review of emerging safety and tolerability data by the Safety Monitoring Committee (SMC). However, PK data is not part of the SMC review, but may be reviewed by a SMC designee at a later time.
Intervention Type
Drug
Intervention Name(s)
Pregabalin 100mg
Other Intervention Name(s)
PGB
Intervention Description
Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.
Intervention Type
Drug
Intervention Name(s)
Acetaminophen 1300mg
Other Intervention Name(s)
Ofirmev
Intervention Description
Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.
Primary Outcome Measure Information:
Title
Treatment Related Adverse Events
Description
The incidence and severity of treatment-emergent adverse events
Time Frame
7 days
Title
Treatment related Drowsiness and Dizziness
Description
The incidence and severity of somnolence and dizziness
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, Cmax
Description
Maximum observed concentration
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, Tmax
Description
Time to maximum observed drug concentration (Tmax)
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, t1/2
Description
Apparent elimination half-life
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-last
Description
Area under the drug concentration-time curve from time zero to the last measurable concentration
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-inf
Description
AUC from time zero to infinity
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, λz
Description
Apparent terminal elimination rate constant
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, CL
Description
Apparent clearance
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, SAD Phase, Vz
Description
Apparent terminal volume of distribution
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, AUCτ
Description
Area under the plasma concentration-time curve during a dosage interval
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Tmax,ss
Description
Time to Cmax at SS
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmax,ss
Description
Maximum concentration at SS
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmin,ss
Description
Minimum concentration at ss
Time Frame
7 dyas
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cav,ss
Description
Average plasma concentration at SS
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Vz, ss
Description
Apparent volume of distribution at SS
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, CLss
Description
Apparent total clearance at SS
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, λz,ss
Description
Apparent first order terminal elimination rate constant at steady state
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, R
Description
Accumulation index
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, LF
Description
Linearity factor
Time Frame
7 days
Title
Plasma PK endpoints for APAP and PGB, multiple doses at steady state
Description
Fluctuation ratio
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female aged 18 to 55 years, inclusive at time of Screening
Body mass index (BMI) between 18.5 and 28.0 kg/m2 inclusive, with a minimum weight of 50 kg and a maximum of 100 kg
Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination, and 12-lead ECG confirming normal sinus rhythm
Negative tests for Hepatitis B surface antigen (HbsAg), hepatitis C virus antibody (anti-HCV), human immunodeficiency virus (HIV)-1 and HIV-2 antibody at Screening
Routine clinical laboratory tests should be within normal limits at Screening and Admission (Day -1) or abnormalities deemed not clinically significant by the Investigator; for liver function tests, AST and ALT values should not be greater than 1.5 times the upper limit of normal range
Negative screen for drugs of abuse or exhibit detectable alcohol levels by breathalyzer at the time of Screening or Admission
Non-smokers or ex-smokers (must have ceased smoking ≥3 months prior Screening visit)
Female subjects:
Must be of non-childbearing potential by surgical sterilization or postmenopausal OR Must not be pregnant, breast feeding, or planning to become pregnant AND must be practicing both a highly effective method of birth control from Screening until at least 90 days after the last dose of study drug.
Women of childbearing potential must have a negative pregnancy test result at Screening and upon admission to the Clinical Trial Unit.
Exclusion Criteria:
Has a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders
Has a history of severe drug allergy, or severe hypersensitivity or severe food allergy, including anaphylaxis or known allergy or sensitivity to any component of PGB or APAP
Has a history of alcoholism or drug abuse
Has acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) at the time of Screening or Admission
Consumption of drugs with enzyme-inducing properties, within 3 weeks prior to the initial dose of study drug and throughout the treatment phase
Has used any prescription medicines, over the counter medicines, or herbal supplements, within 7 days of dosing
Has used any investigational product or participated in any clinical trial within 30 days prior to Screening
Has donated or received any blood or blood products within the 3 months prior to Screening;
Not able to comply with the requirements of this study, including assessments, duration of admission of the study and expected follow up visits
Is unwilling or unable to give written informed consent
Facility Information:
Facility Name
Lotus Clinical Resarch,LLC
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 1 Study to Evaluate Pregabalin and Acetaminophen in Healthy Volunteers
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