Migraines
Conditions
Keywords
pain, neuropathic pain, headaches
Brief summary
To evaluate the safety and tolerability of LY2951742 given as single or multiple subcutaneous injection in healthy male subjects
Interventions
DRUGPlacebo
Administered subcutaneously
DRUGLY2951742
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Are healthy Caucasian males, as determined by medical history and physical examination * Agree to use a reliable method of birth control (e.g. condom AND additional contraception method to be used by respective partner) during the study and for 3 months following the last dose of the investigational product * Have a body mass index (BMI) greater than 19 kilogram/square meter (kg/m\^2) * Have clinical laboratory test results within normal reference range for the population or investigator site * Have venous access sufficient to allow for blood sampling * Are willing to follow study procedures including no drugs (exception of study drug) 72 hours prior to initiation of the laser doppler imaging (LDI) procedure, no chocolate, alcohol or caffeine containing products 12 hours prior to initiation of the laser doppler imaging (LDI) procedure, and complete a 4 hour fast prior to initiation of the laser doppler imaging (LDI) procedure * Have suitable skin characteristics for the dermal capsaicin challenge and have demonstrated a 100 percent increase in dermal flow following capsaicin challenge as part of the screening procedures and measured by laser doppler imaging (LDI)
Exclusion criteria
* Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Are persons who have previously received the investigational product in this study, have completed or withdrawn from this study investigating LY2951742 * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study including QTc greater than 450 milliseconds (msec) (male), history of congenital long QT syndrome or other conduction abnormality * Have abnormal vital signs as determined by the investigator * Have a history or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders (including migraine) that would constitute a risk when taking the study medication; or of interfering with the interpretation of data study * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Show evidence of: 1. Human immunodeficiency virus infection and/or positive human immunodeficiency virus (HIV) antibodies 2. Hepatitis C and/or positive hepatitis C antibody 3. Hepatitis B and/or positive hepatitis B surface antigen * Intend to use over-the-counter or prescription medication that may interfere with study safety assessments or other measurements within 7 days prior to dosing and during the study (example: systemic glucocorticoids, immunomodulatory drugs, drugs with propensity for dermal reactions, and drugs with known liver toxicity). * Have donated blood of more than 500 milliliter (mL) or has undergone major surgery * The use of caffeine containing products and alcohol is not allowed from 12 hours prior to all study visits and during in clinic stays. All other times, alcohol consumption and caffeine intake are limited to no more than 2 alcoholic beverages or equivalent (beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits (25 milliliter \[mL/1 ounce\]) per day and caffeinated beverages will be limited to no more than 2 units per day amounts (1 unit=120 milligrams \[mg\] of caffeine). Strenuous activity is not allowed from 1 week prior to admission until the follow-up visit. * Are smokers within the previous 6 months * Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer)prior to dosing or have received a vaccination within 1 month * Have a history of multiple or severe allergies or has had an anaphylactic reaction or intolerability to prescription or non-prescription drugs or food * Are immunocompromised * Have had cancer or within the past 5 years * Have a history of significant allergies, in particular to ethanol or sensitivity to the fruits of capsicum plants (example: chili peppers) * Have eczema, scleroderma, psoriasis, dermatitis, keloids, tumors, ulcers, burns, flaps, or grafts on their forearm or other abnormality of the skin which may interfere with the study assessments * Cannot avoid excess tanning (any exposure to sunlight or a tanning bed which would cause a sunburn reaction) throughout the study and cannot cover forearms for 24 hours prior to treatment period * Have excessive hair growth on the volar surface of the forearm or subjects currently using lotions, oils, depilatory preparations, or other topical treatments on a regular basis which cannot be discontinued for the duration of the study; subject has used any topical treatments within 7 days of the start of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects | Baseline up to 6 months (study completion) | Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and all other non-serious AEs is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame |
|---|---|
| Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | Day 1 up to Day 84 or early discontinuation |
| Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | Day 1 up to Day 84 or early discontinuation |
| Multiple Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | Day 43 up to Day 57 |
| Multiple Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | Day 43 up to Day 57 |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 mg Single Dose LY2951742 Single dose 1 mg LY2951742 administered subcutaneously. | 7 |
| 5 mg Single Dose LY2951742 Single dose 5 mg LY2951742 administered subcutaneously. | 7 |
| 25 mg Single Dose LY2951742 Single dose 25 mg LY2951742 administered subcutaneously. | 7 |
| 75 mg Single Dose LY2951742 Single dose 75 mg LY2951742 administered subcutaneously. | 7 |
| 200 mg Single Dose LY2951742 Single dose 200 mg LY2951742 administered subcutaneously. | 7 |
| 600 mg Single Dose LY2951742 Single dose 600 mg LY2951742 administered subcutaneously. | 7 |
| Placebo Single Dose Single dose matched placebo administered subcutaneously. | 12 |
| Placebo Multiple Dose Multiple dose matched placebo administered subcutaneously every 2 weeks for 6 weeks (4 doses). | 2 |
| 150 mg Multiple Dose LY2951742 Multiple dose 150 mg LY2951742 administered subcutaneously every 2 weeks for 6 weeks (4 doses). | 7 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 1 mg Single Dose LY2951742 | 5 mg Single Dose LY2951742 | 25 mg Single Dose LY2951742 | 75 mg Single Dose LY2951742 | 200 mg Single Dose LY2951742 | 600 mg Single Dose LY2951742 | Placebo Single Dose | Placebo Multiple Dose | 150 mg Multiple Dose LY2951742 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 11.7 | 29.0 years STANDARD_DEVIATION 7.5 | 31.9 years STANDARD_DEVIATION 14.3 | 30.9 years STANDARD_DEVIATION 10.5 | 37.0 years STANDARD_DEVIATION 14.6 | 33.9 years STANDARD_DEVIATION 13.9 | 30.8 years STANDARD_DEVIATION 10 | 22.5 years STANDARD_DEVIATION 0.7 | 22.4 years STANDARD_DEVIATION 1.6 | 30.2 years STANDARD_DEVIATION 11.1 |
| Race/Ethnicity, Customized White | 7 participants | 7 participants | 7 participants | 7 participants | 7 participants | 7 participants | 12 participants | 2 participants | 7 participants | 63 participants |
| Region of Enrollment Belgium | 7 participants | 7 participants | 7 participants | 7 participants | 7 participants | 7 participants | 12 participants | 2 participants | 7 participants | 63 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 12 Participants | 2 Participants | 7 Participants | 63 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 7 | 5 / 7 | 7 / 7 | 4 / 7 | 7 / 7 | 5 / 7 | 9 / 12 | 2 / 2 | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 12 | 0 / 2 | 0 / 7 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and all other non-serious AEs is located in the Reported Adverse Events module.
Time frame: Baseline up to 6 months (study completion)
Population: Safety Population: All participants who received at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Milligram (mg) Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 1 Milligram (mg) Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 6 participants |
| 5 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 5 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 5 participants |
| 25 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 25 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 7 participants |
| 75 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 75 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 4 participants |
| 200 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 200 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 7 participants |
| 600 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 5 participants |
| 600 mg Single Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| Placebo Single Dose | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 9 participants |
| Placebo Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| Placebo Multiple Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| Placebo Multiple Dose | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 2 participants |
| 150 mg Multiple Dose LY2951742 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| 150 mg Multiple Dose LY2951742 | Number of Participants With Clinically Significant Effects | Other Non-Serious Adverse Events | 7 participants |
Secondary
Multiple Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC)
Time frame: Day 43 up to Day 57
Population: PK Population: All participants who received multiple dose LY2951742 study drug with interpretable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 Milligram (mg) Single Dose LY2951742 | Multiple Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 1806501.8 ng*day/mL | Geometric Coefficient of Variation 20.4 |
Secondary
Multiple Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax)
Time frame: Day 43 up to Day 57
Population: PK Population: All participants who received multiple doses LY2951742 study drug with interpretable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 Milligram (mg) Single Dose LY2951742 | Multiple Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 36846.420 ng/mL | Geometric Coefficient of Variation 14.878 |
Secondary
Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC)
Time frame: Day 1 up to Day 84 or early discontinuation
Population: PK Population: All participants who received single dose LY2951742 study drug with interpretable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 Milligram (mg) Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 4718.4 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 11.6 |
| 5 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 19743.5 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 29.7 |
| 25 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 92310.1 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 32.7 |
| 75 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 263144.2 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 44.7 |
| 200 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 624419.4 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 39.8 |
| 600 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Area Under the Curve (AUC) | 2280259.7 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 9.8 |
Secondary
Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax)
Time frame: Day 1 up to Day 84 or early discontinuation
Population: Pharmacokinetic (PK) Population: All participants who received single dose LY2951742 study drug with interpretable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 Milligram (mg) Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 95.60 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21.26 |
| 5 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 404.61 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34.45 |
| 25 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 1995.35 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44.48 |
| 75 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 5920.79 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.51 |
| 200 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 13750.14 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.72 |
| 600 mg Single Dose LY2951742 | Single Dose Pharmacokinetics of LY2951742 Maximal Concentration (Cmax) | 45039.42 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.52 |