Bioavailability Study of Naloxone 5 Milligrams (mg) Intramuscular (IM) Autoinjector

A PHASE 1 RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, 3-TREATMENT CROSS-OVER STUDY TO EVALUATE RELATIVE BIOAVAILABILITY OF INTRAMUSCULAR INJECTION OF NALOXONE HCL 5 Milligrams (mg) [5mg/0.5 Milliliters (mL] USING A QUICKSHOT™ AUTOINJECTOR COMPARED TO 2 mg NALOXONE INTRAMUSCULAR INJECTION AND 2 mg NALOXONE INTRAVENOUS INJECTION IN HEALTHY ADULT PARTICIPANTS

To compare the plasma concentration (bioavailability) and safety of a single naloxone 5 mg autoinjector intramuscular (IM) injection to a single 2 mg IM injection (an approved safe dose) and to a single 2 mg bolus intravenous (IV) injection (an approved safe dose)

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: NaxRedy ™; Drug: Naloxone Hydrochloride Injection, USP; Drug: Naloxone Hydrochloride Injection, USP

Detailed Description

A randomized, open-label, 3-treatment, 6-sequences, 3-period Williams Square crossover single-dose, relative bioavailability study in healthy adult participants. The study includes Screening period, a Treatment period and a Follow-up contact (SoA). At least twelve (12) participants will be enrolled. If the number of evaluable participants falls below 12, participants may be replaced.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

Age and Sex:

1. Healthy male and/or female participants of non-childbearing potential, who, at the time of screening, are between the ages of 18 and 55 years, inclusive.

   Refer to protocol for reproductive criteria for male and female participants.

   Type of Participant and Disease Characteristics:

2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, 12-lead ECG, and/or clinical laboratory tests.

3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

   Weight:

4. BMI of 17.5 to 30.5 kg/m2; and a total body weight > 50 kg (110 lb).

Informed Consent:

5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

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Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions:

1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
2. Current or past diagnosis of any type of drug dependence within the past year will not be eligible to participate. History of alcohol abuse, dependence or binge drinking and/or any other illicit drug use within 6 months of screening. Binge drinking is hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
3. If fever is present within 7 days of admission or screening.
4. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
5. History of HIV infection, hepatitis B, or hepatitis C, positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.

6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

   Prior/Concomitant Therapy:

7. Use of prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention. Prior/Concurrent Clinical Study Experience:

8. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).

   Diagnostic Assessments:

9. A positive urine drug test.
10. Has participated in, is currently participating in, or is seeking treatment for substance-and/or alcohol-related disorders (excluding nicotine and caffeine).
11. Has a positive alcohol breathalyzer test at screening or upon admission to the study center of Treatment Period. Positive results may be repeated and/or participants re-scheduled at the investigator's discretions.
12. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. Repeated BP tests should be spaced at least 5 minutes apart.
13. Screening supine 12-lead ECG demonstrating a QTc interval > 450 msec or a QRS interval > 120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility.

14. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:

    Abnormal platelet count and/or PT/INR; AST or ALT level ≥1.5 × ULN; Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

    Other Exclusions:

15. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
16. History of sensitivity to heparin or heparin-induced thrombocytopenia.
17. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
18. History of hypersensitivity to naloxone or any of the components in the formulation of the study products.

19. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: naloxone 5 mg IM autoinjector; participants will receive in random order, a single naloxone 5 mg IM autoinjector injection into the lateral thigh	Drug: NaxRedy ™; 5 mg (5 mg/0.5 mL) IM autoinjector injection into lateral thigh
Active Comparator: naloxone 2 mg IM; participants will receive in random order, a single naloxone 2 mg IM injection into the gluteus muscle	Drug: Naloxone Hydrochloride Injection, USP; 2 mg IM (2mg/2 mL) injection into gluteal muscle; Drug: Naloxone Hydrochloride Injection, USP; 2 mg bolus IV (2mg/2 mL)
Active Comparator: naloxone 2mg bolus IV; participants will receive in random order, a single naloxone 2 mg bolus IV injection	Drug: Naloxone Hydrochloride Injection, USP; 2 mg IM (2mg/2 mL) injection into gluteal muscle; Drug: Naloxone Hydrochloride Injection, USP; 2 mg bolus IV (2mg/2 mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma naloxone concentration (Cmax) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection	Comparison of bioavailability	predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
Area under the naloxone concentration versus time curve (AUC) from time zero to the last collection time (AUClast) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection	Comparison of bioavailability	predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC from time zero to 2.5 minutes (AUC0-2.5)	Pharmacokinetics all treatment arms	predose and 2.5 minutes after dose
AUC from time zero to 5 minutes (AUC0-5)	Pharmacokinetics all treatment arms	predose, 2.5 and 5 minutes after dose
AUC from time zero to 15 minutes (AUC0-15)	Pharmacokinetics all treatment arms	predose, 2.5, 5, 10 and 15 minutes after dose
AUC from time zero to 30 minutes (AUC0-30)	Pharmacokinetics all treatment arms	predose, 2.5, 5, 10, 15, and 30 minutes after dose
AUC from time zero extrapolated to infinity (AUCinf) [if data permit]	Pharmacokinetics all treatment arms	predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Time to maximum observed naloxone plasma concentration (Tmax) [if data permit],	Pharmacokinetics all treatment arms	predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Time for naloxone plasma concentration to decrease by one half (t1/2) [if data permit].	Pharmacokinetics all treatment arms	predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Number of participants with a clinically significant change from baseline physical examination	Safety and tolerability all treatments	baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline vital signs	Safety and tolerability all treatments	baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline clinical safety laboratory measurements	Safety and tolerability all treatment arms	baseline to 28 days after last dose
Number of participants with clinically significant AEs from baseline	Safety and tolerability all treatment arms	baseline to 28 days after last dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Actual): January 8, 2021
• Study Completion (Actual): January 8, 2021

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; healthy volunteers; naloxone; intramuscular; high dose; cross-over study; autoinjector; 5 mg; 3 treatment arms
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: C2431001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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