Pain
Conditions
Keywords
comparison
Brief summary
The purpose of this study is to evaluate two experimental pain models to see if they would be useful for comparing different products for reduction in pain intensity. The models evaluated were the ultraviolet-B (UVB) burn and intradermal capsaicin experimental pain models. Medications compared were a single dose each, of intravenous (IV) acetaminophen, oral acetaminophen, placebo, and IV morphine.
Interventions
DRUGIV Acetaminophen (Treatment A)
Acetaminophen administered by intravenous (IV) infusion
DRUGOral Acetaminophen (Treatment B)
Acetaminophen administered by oral tablets
Placebo administered by IV infusion or oral tablets
OTHERMorphine (Treatment D)
Morphine administered by IV infusion
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Must have a health status of healthy assessed by the investigator and defined as no clinically significant deviation from normal medical history, physical examination, vital signs, and clinical laboratory determinations. 2. Must be male, Caucasian, between 18 and 55 years of age (inclusive) at the time of the screening. 3. Must have a body mass index (BMI) ≥ 19.0 and ≤ 30.0 kg/m2 with a minimum weight of 110 pounds (50 kg) at screening.
Exclusion criteria
1. A positive test result for human immunodeficiency virus (HIV), hepatitis B (surface antigen), or hepatitis C virus antibody at Screening. 2. A history of any drug allergy, hypersensitivity, or intolerance to acetaminophen, morphine, or capsaicin or to any of the excipients in the IV or oral formulations used. 3. A positive test result for drugs of abuse, alcohol, or cotinine. 4. Fitzpatrick Skin Type V or VI (based on a Skin Type score of greater than 30. 5. A history of conditions which might be specifically contraindicated or require caution to be used during the administration of any drug in the study. 6. Any other medical, psychiatric and/or social reason for exclusion as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model | within 6 hours | The UVB burn pain model is a validated screening tool for pain killers in clinical drug development. A temperature of 50 degrees centigrade (°C) is used to burn the participant for 5 seconds. Then the participant rates his pain on a scale from 0 (no pain) to 10 (most intense pain). That score is recorded as baseline. Then the participant rates his pain again six hours after taking the assigned medication. The average at baseline is subtracted from the average at hour 6. Because this is a measure of reduction in pain intensity, a higher score is better (it means there is more pain relief). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | within 6 hours | Participants rated their pain intensity on a scale of 0 (no pain) to 10 (most intense pain). The observed mean and standard deviation are disclosed through Hour 6 |
Countries
United States
Participant flow
Recruitment details
A total of 79 participants were enrolled in the study. 12 participants in Part 1 and 66 participants in Part 2 were randomized to sequence, and received at least one dose of the study treatment.
Pre-assignment details
One participant in Part 2 was randomized but discontinued without receiving treatment due to an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 All participants who received a drug product in Part 1 | 12 |
| Part 2 All participants who received a drug product in Part 2 | 66 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part 1 | Withdrawal by Subject | 1 |
| Part 2 | Adverse Event | 2 |
| Part 2 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Part 1 | Total | Part 2 |
|---|---|---|---|
| Age, Continuous | 28.9 years | 26.9 years | 26.5 years |
| Race/Ethnicity, Customized Race, White Hispanic or Latino | 0 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Race, White Not Hispanic or Latino | 12 Participants | 72 Participants | 60 Participants |
| Region of Enrollment United States | 12 Participants | 78 Participants | 66 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 78 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 64 | 0 / 65 | 0 / 65 | 0 / 64 |
| other Total, other adverse events | 2 / 12 | 2 / 12 | 4 / 12 | 8 / 12 | 10 / 64 | 12 / 65 | 14 / 65 | 38 / 66 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 64 | 0 / 65 | 0 / 65 | 0 / 64 |
Outcome results
Primary
Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model
The UVB burn pain model is a validated screening tool for pain killers in clinical drug development. A temperature of 50 degrees centigrade (°C) is used to burn the participant for 5 seconds. Then the participant rates his pain on a scale from 0 (no pain) to 10 (most intense pain). That score is recorded as baseline. Then the participant rates his pain again six hours after taking the assigned medication. The average at baseline is subtracted from the average at hour 6. Because this is a measure of reduction in pain intensity, a higher score is better (it means there is more pain relief).
Time frame: within 6 hours
Population: Completers, defined as participants who were enrolled in the study, took the entire dose of all study drugs, and provided all pain intensity assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen | Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model | 0.73 score on a scale | Standard Deviation 1.104 |
| Oral Acetaminophen | Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model | -0.64 score on a scale | Standard Deviation 1.804 |
| Placebo | Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model | -0.36 score on a scale | Standard Deviation 1.567 |
| Morphine | Part 1: Change From Baseline in Pain Intensity at Hour 6 Using the Thermal Suprathreshold Pain in the Ultraviolet-B (UVB) Burn Pain Model | 0.36 score on a scale | Standard Deviation 1.206 |
Secondary
Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area
Participants rated their pain intensity on a scale of 0 (no pain) to 10 (most intense pain). The observed mean and standard deviation are disclosed through Hour 6
Time frame: within 6 hours
Population: Per-Protocol Population, defined as participants who were enrolled in the study, have taken the entire dose of all study drugs, and provided all pain intensity assessments designed for the UVB Burn Pain Model without a major protocol deviation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.25 Hours | 5.2 scores on a scale | Standard Deviation 1.39 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 4 Hours | 5.5 scores on a scale | Standard Deviation 1.17 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 6 Hours | 5.6 scores on a scale | Standard Deviation 1.32 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | Baseline | 5.4 scores on a scale | Standard Deviation 1.3 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.5 Hours | 5.0 scores on a scale | Standard Deviation 1.34 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.75 Hours | 5.0 scores on a scale | Standard Deviation 1.37 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 1 Hour | 5.0 scores on a scale | Standard Deviation 1.44 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 2 Hours | 5.3 scores on a scale | Standard Deviation 1.13 |
| IV Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 3 Hours | 5.4 scores on a scale | Standard Deviation 1.3 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 3 Hours | 5.2 scores on a scale | Standard Deviation 1.44 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.5 Hours | 5.1 scores on a scale | Standard Deviation 1.36 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | Baseline | 5.5 scores on a scale | Standard Deviation 1.4 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.75 Hours | 5.1 scores on a scale | Standard Deviation 1.3 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 1 Hour | 4.9 scores on a scale | Standard Deviation 1.23 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 4 Hours | 5.4 scores on a scale | Standard Deviation 1.4 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.25 Hours | 5.3 scores on a scale | Standard Deviation 1.48 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 6 Hours | 5.5 scores on a scale | Standard Deviation 1.3 |
| Oral Acetaminophen | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 2 Hours | 5.1 scores on a scale | Standard Deviation 1.26 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.25 Hours | 5.5 scores on a scale | Standard Deviation 1.28 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 1 Hour | 5.2 scores on a scale | Standard Deviation 1.34 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.5 Hours | 5.3 scores on a scale | Standard Deviation 1.28 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 6 Hours | 5.5 scores on a scale | Standard Deviation 1.34 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 2 Hours | 5.6 scores on a scale | Standard Deviation 1.28 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 4 Hours | 5.5 scores on a scale | Standard Deviation 1.3 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.75 Hours | 5.4 scores on a scale | Standard Deviation 1.26 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | Baseline | 5.5 scores on a scale | Standard Deviation 1.32 |
| Placebo | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 3 Hours | 5.5 scores on a scale | Standard Deviation 1.23 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 6 Hours | 5.4 scores on a scale | Standard Deviation 1.45 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | Baseline | 5.6 scores on a scale | Standard Deviation 1.4 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.25 Hours | 4.9 scores on a scale | Standard Deviation 1.56 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.5 Hours | 4.7 scores on a scale | Standard Deviation 1.5 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 0.75 Hours | 4.7 scores on a scale | Standard Deviation 1.62 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 1 Hour | 4.6 scores on a scale | Standard Deviation 1.55 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 3 Hours | 5.0 scores on a scale | Standard Deviation 1.67 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 4 Hours | 5.2 scores on a scale | Standard Deviation 1.42 |
| Morphine | Part 2: Observed Thermal Suprathreshold Pain Intensity in the UVB Burn Area | 2 Hours | 5.1 scores on a scale | Standard Deviation 1.5 |