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

Postoperative Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04265456
• Other study ID #: CP-NVK009-0004
• Status: Completed
• Phase: Phase 1
• Start date: January 14, 2020
• Est. completion date: July 22, 2020

Study information

• Verified date: August 2020
• Source: Nevakar, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: July 22, 2020
• Est. primary completion date: June 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Pregabalin 100mg
Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.
• Acetaminophen 1300mg
Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.

Locations

Country	Name	City	State
United States	Lotus Clinical Resarch,LLC	Pasadena	California

Sponsors (1)

Lead Sponsor	Collaborator
Nevakar, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Related Adverse Events	The incidence and severity of treatment-emergent adverse events	7 days
Primary	Treatment related Drowsiness and Dizziness	The incidence and severity of somnolence and dizziness	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, Cmax	Maximum observed concentration	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, Tmax	Time to maximum observed drug concentration (Tmax)	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, t1/2	Apparent elimination half-life	7 days
Secondary	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
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-inf	AUC from time zero to infinity	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, ?z	Apparent terminal elimination rate constant	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, CL	Apparent clearance	7 days
Secondary	Plasma PK endpoints for APAP and PGB, SAD Phase, Vz	Apparent terminal volume of distribution	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, AUCt	Area under the plasma concentration-time curve during a dosage interval	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Tmax,ss	Time to Cmax at SS	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmax,ss	Maximum concentration at SS	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmin,ss	Minimum concentration at ss	7 dyas
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cav,ss	Average plasma concentration at SS	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Vz, ss	Apparent volume of distribution at SS	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, CLss	Apparent total clearance at SS	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, ?z,ss	Apparent first order terminal elimination rate constant at steady state	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, R	Accumulation index	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state, LF	Linearity factor	7 days
Secondary	Plasma PK endpoints for APAP and PGB, multiple doses at steady state	Fluctuation ratio	7 days