Head Lice
Conditions
Brief summary
This clinical study is designed to evaluate the clinical (therapeutic) effect of a generic ivermectin lotion 0.5% (Actavis Laboratories UT, Inc.) relative to that of the Food and Drug Administration (FDA) Reference Listed Drug (RLD) SKLICE® (ivermectin) lotion, 0.5% (Arbor Pharmaceuticals, LLC) in participants with active head lice infestation. Additionally, both the test and reference (that is; the RLD) treatments were tested for superiority to a placebo.
Detailed description
Participants will be randomized by household in a 3:3:1 ratio to receive generic ivermectin lotion 0.5%, Sklice (ivermectin) lotion 0.5%, or vehicle lotion.
Interventions
DRUGGeneric Ivermectin Lotion 0.5%
Topical lotion, generic formulation of the brand product.
DRUGSklice® (Ivermectin) Lotion 0.5%
Topical lotion, brand product.
DRUGVehicle Lotion
Topical lotion, placebo. Has no active ingredient.
Sponsors
Teva Pharmaceuticals USA
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Signed Institutional Review Board (IRB)-approved informed consent form that meets all criteria of current FDA regulations. For participants who are considered minors in the state the study is being conducted (\<18 years in most states), the parent or legal guardian should sign the consent form and the child will be required to sign a participant assent form, as appropriate. Participants 11-17 years of age will read and sign an IRB-approved assent form and participants 6-10 years of age will provide verbal assent. Participants 6 months-5 years of age will be exempt from providing assent based on the child's comprehension and cognitive skills. 2. The participant and/or the participant's parent (legal guardian) is willing to apply the study product as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study. 3. Male or non-pregnant, non-lactating female, 6 months of age or older. 4. Females of childbearing potential must not be pregnant or lactating at Visit 1 (Day -1 to 1) (as confirmed by a negative urine pregnancy test with a sensitivity of less than 50 milli-international units/milliliter \[mIU/mL\] or equivalent units of human chorionic gonadotropin). Women of childbearing potential must agree to the use of a reliable method of contraception. (for example, total abstinence, intrauterine device, a double-barrier method, oral, transdermal, injected, or implanted non-hormonal or hormonal contraceptive) throughout the study. Female participants using hormonal contraceptives should have been on the same product/dosing regimen for at least 28 days before Visit 1 (Day -1 to 1) and should not change this regimen during the study. A sterile sexual partner is not considered an adequate form of birth control. 5. Index participants (that is, the youngest household member) must have an active head lice infestation, defined as ≥3 live lice (that is, live adults and/or nymphs), at Visit 1 (Day -1 to 1). 6. Household members participating in the study must have ≥1 live louse (that is; live adults and/or nymphs) at Visit 1 (Day -1 to 1). 7. All members of the household must be present for examination. Any male head of household who is unable to attend Visit 1 (Day -1 to 1) may be assessed by a second member of the household as being lice free.
Exclusion criteria
1. Females who are pregnant, lactating or planning to become pregnant during the study period. 2. Participants who do not have a known household affiliation with their household members (that is, do not stay in 1 household consistently, sleeping at 1 place several nights and then at another place or location). Household is defined as living in a shared area or space (for example the same house or apartment unit). 3. Any infested member of the household is unable or unwilling to be treated with the study product. This includes male heads of household who do not attend Visit 1 (Day -1 to 1) but report infestation with lice. 4. More than 3 members of the household infested with lice. 5. Presence of visible skin/scalp condition(s) or open wounds at the application site that are not attributable to head lice infestation and that in the opinion of the Investigator will interfere with safety and/or efficacy evaluations. 6. Presence of eczema or atopic dermatitis at the application site. 7. Use of any prescription, over-the-counter, or home remedies for the treatment of head lice within 7 days before Visit 1 (Day -1 to 1). 8. Use of pediculicides within 4 weeks before Visit 1 (Day -1 to 1). 9. Use of systemic anti-parasitic agents within four weeks before Visit 1. 10. Participants with very short (shaved) hair or who are planning to shave head during the study. 11. Use of any hair dye, bleaches, hair straightening, or permanent wave solution on the hair within 14 days before Visit 1 (Day -1 to 1). 12. History of allergy or sensitivity to pediculicides or hair care products. 13. History of any drug hypersensitivity or intolerance that, in the opinion of the Investigator, would compromise the safety of the participant or results of the study. 14. Significant history or current acute or chronic infectious disease, system disorder, Netherton's Syndrome, organ disorder (for example, hepatic or renal impairment) or insufficiency, immunosuppression (from medical treatment or disease), organ transplant, uncontrolled diabetes, uncontrolled hypertension, current ocular condition, or other medical condition that, in the Investigator's opinion, would place the study participant at undue risk by participating in the study. 15. Participants or non-infested household members who would act as the primary caregiver who are of intellectually competent age but unable to understand the protocol requirements, instructions, and study-related restrictions, the nature, scope, and possible consequences of the clinical study. 16. Receipt of any drug as part of a research study within 30 days before Visit 1 (Day -1 to 1). 17. The participant is a member of the investigational study staff or a member of the family of the investigational study staff. 18. Previous participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Index Participants Who Were Considered a Treatment Success: PP Population | Day 15 ± 2 | Treatment success was defined as the absence of live lice. Index participant was defined as the youngest household member who was randomized into the study. Therapeutic equivalence evaluation between test (generic ivermectin lotion 0.5%) and reference groups (Sklice \[ivermectin\] lotion 0.5%) was done in this endpoint, hence placebo group was not included. |
| Percentage of Index Participants Who Were Considered a Treatment Success: mITT Population | Day 15 ± 2 | Treatment success was defined as the absence of live lice. Index participant was defined as the youngest household member who was randomized into the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: PP Population | Day 15 ± 2 | Treatment success was defined as the absence of live lice. Non-index participant: Any household member who agreed to participate in the study but was not the youngest household member. Index participant: The youngest household member who was randomized into the study. Therapeutic equivalence evaluation between test (generic ivermectin lotion 0.5%) and reference groups (Sklice \[ivermectin\] lotion 0.5%) was done in this endpoint, hence placebo group was not included. |
| Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: mITT Population | Day 15 ± 2 | Treatment success was defined as the absence of live lice. Non-index participant: Any household member who agreed to participate in the study but was not the youngest household member. Index participant: The youngest household member who was randomized into the study. |
Countries
United States
Participant flow
Recruitment details
A total of 912 infested household participants were included and 911 (905 enrolled \[380 index + 525 non-index\] + 6 non-enrolled) were treated. Participants were randomized in 3:3:1 to generic ivermectin, Sklice (ivermectin), or vehicle lotion. 1 participant was considered randomized but not dispensed, so not included in any treatment arm.
Pre-assignment details
Non-enrolled infested participants: Any household member who was infested with lice and agreed to be treated with study drug but did not participate in the study. 912 infested patients were available to participate in the study, one patient was not dispensed study product, 911 patients (905 enrolled + 6 non-enrolled) were treated.
Participants by arm
| Arm | Count |
|---|---|
| Generic Ivermectin Lotion 0.5% Infested household participants administered a single application of up to 117 grams (1 tube) of generic ivermectin 0.5% topical lotion to dry hair (avoiding contact with eyes) at home on Day 1, left the lotion on the hair and scalp for 10 minutes, and then rinsed off with warm water. Participants were instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel was permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants were not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit had been completed. | 399 |
| Sklice (Ivermectin) Lotion Infested household participants administered a single application of up to 117 grams (1 tube) of Sklice ivermectin 0.5% topical lotion to dry hair (avoiding contact with eyes) at home on Day 1, left the lotion on the hair and scalp for 10 minutes, and then rinsed off with warm water. Participants were instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel was permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants were not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit had been completed. | 400 |
| Vehicle Lotion Infested household participants administered a single application of up to 117 grams (1 tube) of vehicle topical lotion to dry hair (avoiding contact with eyes) at home on Day 1, left the lotion on the hair and scalp for 10 minutes, and then rinsed off with warm water. Participants were instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel was permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants were not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit had been completed. | 112 |
| Total | 911 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 11 | 3 |
| Overall Study | Need alternate therapy due to live lice | 17 | 25 | 81 |
| Overall Study | Other than specified | 5 | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 4 | 0 |
Baseline characteristics
| Characteristic | Generic Ivermectin Lotion 0.5% | Sklice (Ivermectin) Lotion | Vehicle Lotion | Total |
|---|---|---|---|---|
| Age, Continuous | 18.8 years STANDARD_DEVIATION 15.4 | 16.8 years STANDARD_DEVIATION 13.9 | 19.0 years STANDARD_DEVIATION 14.4 | 18.2 years STANDARD_DEVIATION 14.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 344 Participants | 346 Participants | 93 Participants | 783 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 54 Participants | 19 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of live lice | 4.9 live lice STANDARD_DEVIATION 4.4 | 4.4 live lice STANDARD_DEVIATION 3.5 | 4.5 live lice STANDARD_DEVIATION 3.1 | 4.6 live lice STANDARD_DEVIATION 3.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 12 Participants | 3 Participants | 26 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 377 Participants | 377 Participants | 106 Participants | 860 Participants |
| Sex: Female, Male Female | 322 Participants | 324 Participants | 97 Participants | 743 Participants |
| Sex: Female, Male Male | 77 Participants | 76 Participants | 15 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 399 | 0 / 400 | 0 / 112 |
| other Total, other adverse events | 31 / 399 | 21 / 400 | 1 / 112 |
| serious Total, serious adverse events | 0 / 399 | 0 / 400 | 0 / 112 |
Outcome results
Primary
Percentage of Index Participants Who Were Considered a Treatment Success: mITT Population
Treatment success was defined as the absence of live lice. Index participant was defined as the youngest household member who was randomized into the study.
Time frame: Day 15 ± 2
Population: Index participants in mITT population. mITT population included all randomized participants who met all inclusion/exclusion criteria, applied the study product as instructed, and returned for at least 1 post-baseline evaluation visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Generic Ivermectin Lotion 0.5% | Percentage of Index Participants Who Were Considered a Treatment Success: mITT Population | 91.7 percentage of participants |
| Sklice (Ivermectin) Lotion | Percentage of Index Participants Who Were Considered a Treatment Success: mITT Population | 89.7 percentage of participants |
| Vehicle Lotion | Percentage of Index Participants Who Were Considered a Treatment Success: mITT Population | 28.6 percentage of participants |
Comparison: Analysis was performed using Cochran- Mantel-Haenszel test, stratified by clinical site in mITT population (using last observation carried forward \[LOCF\] method).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Analysis was performed using Cochran- Mantel-Haenszel test, stratified by clinical site in mITT population (using LOCF method).p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Percentage of Index Participants Who Were Considered a Treatment Success: PP Population
Treatment success was defined as the absence of live lice. Index participant was defined as the youngest household member who was randomized into the study. Therapeutic equivalence evaluation between test (generic ivermectin lotion 0.5%) and reference groups (Sklice \[ivermectin\] lotion 0.5%) was done in this endpoint, hence placebo group was not included.
Time frame: Day 15 ± 2
Population: Index participants in PP population. PP population: randomized participants who met all eligibility criteria, applied study drug, were treatment successes/failures and made the final study visit ( Day 15 ± 2), and had no significant protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Generic Ivermectin Lotion 0.5% | Percentage of Index Participants Who Were Considered a Treatment Success: PP Population | 90.9 percentage of participants |
| Sklice (Ivermectin) Lotion | Percentage of Index Participants Who Were Considered a Treatment Success: PP Population | 89.0 percentage of participants |
Comparison: If the 90% confidence interval (CI) for the absolute difference between the percentage of participants who were considered a treatment success in the generic ivermectin lotion and sklice (ivermectin) lotion was contained within the range (-20%, +20%) then therapeutic equivalence of the generic ivermectin lotion and sklice (ivermectin) lotion was considered to have been demonstrated.90% CI: [-3.9, 7.8]
Secondary
Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: mITT Population
Treatment success was defined as the absence of live lice. Non-index participant: Any household member who agreed to participate in the study but was not the youngest household member. Index participant: The youngest household member who was randomized into the study.
Time frame: Day 15 ± 2
Population: mITT population included all randomized participants who met all inclusion/exclusion criteria, applied the study product as instructed, and returned for at least one post-baseline evaluation visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Generic Ivermectin Lotion 0.5% | Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: mITT Population | 92.2 percentage of participants |
| Sklice (Ivermectin) Lotion | Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: mITT Population | 91.3 percentage of participants |
| Vehicle Lotion | Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: mITT Population | 25.2 percentage of participants |
Comparison: Analysis was performed using Cochran- Mantel-Haenszel test, stratified by clinical site in mITT population (using LOCF method).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Analysis was performed using Cochran- Mantel-Haenszel test, stratified by clinical site in mITT population (using LOCF method).p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: PP Population
Treatment success was defined as the absence of live lice. Non-index participant: Any household member who agreed to participate in the study but was not the youngest household member. Index participant: The youngest household member who was randomized into the study. Therapeutic equivalence evaluation between test (generic ivermectin lotion 0.5%) and reference groups (Sklice \[ivermectin\] lotion 0.5%) was done in this endpoint, hence placebo group was not included.
Time frame: Day 15 ± 2
Population: PP population: randomized participants who met all eligibility criteria, applied study drug, were treatment successes/failures and made the final study visit (Day 15 ± 2), and had no significant protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Generic Ivermectin Lotion 0.5% | Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: PP Population | 91.6 percentage of participants |
| Sklice (Ivermectin) Lotion | Percentage of All Randomized (Index + Non-Index) Participants Who Were Considered a Treatment Success: PP Population | 90.7 percentage of participants |
Comparison: If the 90% CI for the absolute difference between the percentage of participants who were considered a treatment success in the generic ivermectin lotion and sklice (ivermectin) lotion was contained within the range (-20%, +20%) then therapeutic equivalence of the generic ivermectin lotion and sklice (ivermectin) lotion was considered to have been demonstrated.90% CI: [-2.6, 4.5]