A Phase 1 Study to Evaluate Pregabalin and Acetaminophen in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Pregabalin 100mg; Drug: Acetaminophen 1300mg

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Resarch,LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1300 mg Acetaminophen and 100 mg IV Pregabalin; 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).	Drug: Pregabalin 100mg; Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.; Other Names: PGB; Drug: Acetaminophen 1300mg; Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.; Other Names: Ofirmev
No Intervention: Placebo; Saline solution
Experimental: 1300 mg Acetaminophen and 100 mg +/- 25 IV Pregabalin; 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.	Drug: Pregabalin 100mg; Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.; Other Names: PGB; Drug: Acetaminophen 1300mg; Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.; Other Names: Ofirmev

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Related Adverse Events	The incidence and severity of treatment-emergent adverse events	7 days
Treatment related Drowsiness and Dizziness	The incidence and severity of somnolence and dizziness	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma PK endpoints for APAP and PGB, SAD Phase, Cmax	Maximum observed concentration	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, Tmax	Time to maximum observed drug concentration (Tmax)	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, t1/2	Apparent elimination half-life	7 days
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	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-inf	AUC from time zero to infinity	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, λz	Apparent terminal elimination rate constant	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, CL	Apparent clearance	7 days
Plasma PK endpoints for APAP and PGB, SAD Phase, Vz	Apparent terminal volume of distribution	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, AUCτ	Area under the plasma concentration-time curve during a dosage interval	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Tmax,ss	Time to Cmax at SS	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmax,ss	Maximum concentration at SS	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmin,ss	Minimum concentration at ss	7 dyas
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cav,ss	Average plasma concentration at SS	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Vz, ss	Apparent volume of distribution at SS	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, CLss	Apparent total clearance at SS	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, λz,ss	Apparent first order terminal elimination rate constant at steady state	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, R	Accumulation index	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state, LF	Linearity factor	7 days
Plasma PK endpoints for APAP and PGB, multiple doses at steady state	Fluctuation ratio	7 days

Collaborators and Investigators

• Sponsor: Nevakar, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): July 22, 2020

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Acetaminophen; Pregabalin
• Other Study ID Numbers: CP-NVK009-0004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No