Pharmacokinetics
Conditions
Brief summary
This study is to determine the pharmacokinetics (how the body absorbs, breaks down and eliminates drug from your body) of nalmefene when given intranasally (IN;into the nose) compared to a dose of nalmefene when given intramuscularly (IM; into the muscle); to compare the blood levels of nalmefene when given IN to nalmefene when given IM; and to evaluate the safety and tolerability of nalmefene IN.
Detailed description
Open-label, randomized, 2-period, 2-treatment, 2-sequence, crossover study in 68 healthy volunteers. Subjects will be assigned to each of the 2 possible sequences. Each subject will receive 2 treatments during the 2 dosing periods: Intranasal (IN) dose of 3 mg nalmefene hydrochloride and intramuscular (IM) dose of 1.0 mg nalmefene, with a 4 day washout period between doses. Screening can occur up to 28 days before baseline admission, subjects will then stay in the inpatient facility for 7 days to complete the treatment phase of the study and will be discharged following completion of the discharge procedures at the end of the last period. Subjects will be called 3 to 5 days after discharge to inquire concerning Adverse Events (AEs) and concomitant medications since discharge.
Interventions
3mg nasal spray
DRUGNalmefene
1mg intramuscular injection
Sponsors
Opiant Pharmaceuticals Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged 18 to 55 years inclusive * BMI ranging from 18 to 30 kg/m2, inclusive * Adequate venous access * Subjects must be non-smokers
Exclusion criteria
* History of clinically significant disease * Significant trauma injury, major surgery, open biopsy within 30 days prior to screening * Following an abnormal diet 4 weeks prior to screening * Use of over the counter medications, dietary supplements, herbal products, vitamins or opioid analgesics 14 days before intervention * Use of enzyme altering drugs 30 days before intervention * Use of nasal products 28 days before intervention and throughout the study * Previous or current opioid, alcohol, or other drug dependence * Donated or received blood 30 days before intervention * Women who are pregnant or breastfeeding at screening * Women of childbearing potential unless surgically sterile or use effective contraception * Current or recent upper respiratory tract infection * Allergic to nalmefene
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 48 hours | Maximum concentration of plasma nalmefene comparing IN to IM |
| Time to Maximum Plasma Concentration (Tmax) | 48 hours | Time to maximum concentration of plasma nalmefene comparing IN to IM |
| Area Under the Curve (AUC-inf) | 48 hours | Area under the curve of plasma nalmefene comparing IN to IM |
| Half-life (t1/2) | 48 hours | Half life of plasma nalmefene comparing IN to IM |
Countries
United States
Participant flow
Recruitment details
Complete
Participants by arm
| Arm | Count |
|---|---|
| Intranasal Nalmefene Then Intramuscular Nalmefene 3 mg nalmefene hydrochloride intranasally (1 spray) then 1 mg nalmefene hydrochloride solution intramuscularly (single dose) | 34 |
| Intramuscular Nalmefene Then Intranasal Nalmefene 1 mg nalmefene hydrochloride solution intramuscularly (single dose) then 3 mg nalmefene hydrochloride intranasally (1 spray) | 34 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (7 Days) | Physician Decision | 0 | 1 |
| Washout (7 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Intranasal Nalmefene Then Intramuscular Nalmefene | Intramuscular Nalmefene Then Intranasal Nalmefene | Total |
|---|---|---|---|
| Age, Customized Age 18 to 55 years old | 34 Participants | 34 Participants | 68 Participants |
| BMI | 26.58 kg/m2 STANDARD_DEVIATION 2.54 | 25.60 kg/m2 STANDARD_DEVIATION 2.996 | 26.09 kg/m2 STANDARD_DEVIATION 2.8 |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 12 Participants | 23 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other specific islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 20 Participants | 41 Participants |
| Region of Enrollment United States | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 10 Participants | 18 Participants | 28 Participants |
| Sex: Female, Male Male | 24 Participants | 16 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 68 |
| other Total, other adverse events | 42 / 66 | 8 / 68 |
| serious Total, serious adverse events | 0 / 66 | 0 / 68 |
Outcome results
Primary
Area Under the Curve (AUC-inf)
Area under the curve of plasma nalmefene comparing IN to IM
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Nalmefene | Area Under the Curve (AUC-inf) | 41.5 hour*ng/mL | Standard Deviation 8.45 |
| Intramuscular Nalmefene | Area Under the Curve (AUC-inf) | 17.0 hour*ng/mL | Standard Deviation 3.13 |
Primary
Half-life (t1/2)
Half life of plasma nalmefene comparing IN to IM
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Nalmefene | Half-life (t1/2) | 11.4 hour | Standard Deviation 2.37 |
| Intramuscular Nalmefene | Half-life (t1/2) | 10.6 hour | Standard Deviation 1.95 |
Primary
Maximum Plasma Concentration (Cmax)
Maximum concentration of plasma nalmefene comparing IN to IM
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Nalmefene | Maximum Plasma Concentration (Cmax) | 12.2 ng/ml | Standard Deviation 6.71 |
| Intramuscular Nalmefene | Maximum Plasma Concentration (Cmax) | 1.77 ng/ml | Standard Deviation 1.18 |
Primary
Time to Maximum Plasma Concentration (Tmax)
Time to maximum concentration of plasma nalmefene comparing IN to IM
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Nalmefene | Time to Maximum Plasma Concentration (Tmax) | 0.25 hours |
| Intramuscular Nalmefene | Time to Maximum Plasma Concentration (Tmax) | 0.333 hours |