Phase 3 Trial to Assess the Safety and Efficacy of Natroba for the Treatment of Scabies
Study Details
Study Description
Brief Summary
To assess the safety and efficacy of Natroba (spinosad) topical suspension versus placebo for the complete cure of scabies after a single treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a double blind, two-arm, 28-day, placebo-controlled study with approximately 120 infested "index" subjects randomized 1:1 to Natroba™ or Placebo. All members of a household (no more than 6 individuals) with a suspected "index" subject must be screened at the first visit. In this study, "index" subjects are defined as the youngest infested household member (≥4 years). If the members have an active scabies infestation and meet all other criteria, they must agree to participate in the study. Household members who do not present with scabies at the screening visit must also agree to apply the same blinded investigational product (IP) as household members who present with scabies. All infested household members must agree to participate in the study or none will be enrolled. Screening procedures include informed consent, medication and medical history, urine pregnancy test for females of childbearing potential, scabies assessment (visual evidence of burrows, inflammatory/non-inflammatory lesions and pruritus), microscopic examination of skin scraping, or dermatoscopy, to demonstrate the presence of mites, eggs, and/or scybala (dermatoscopy must confirm burrows), vital signs, general skin and eye assessment, randomization, and IP dispensing and instruction.
After screening on Day 1, all randomized subjects will be dispensed IP (Natroba™ or Placebo) to apply at home later the same day as a single treatment over the entire body from the neck down to the toes (including the soles of the feet) and to the scalp (if balding) or hairline, temples and forehead on the same day. Subjects less than 12 years of age should be assisted with administration by a parent, guardian or caregiver. Subjects will rub the treatment into the skin followed by a 10-minute wait period before getting dressed. Showering or bathing must not occur earlier than 6 hours after treatment and no later than at least 1 hour prior to Day 2 visit.
On Day 2 (Visit 2), all household members will return for general skin and eye assessments of possible irritation, and to confirm that all IP was left on for a minimum of 6 hours before bathing or showering. If a subject reports an adverse event assessed as related by the PI on Day 2 (Visit 2) then a follow-up visit with the investigator must be scheduled within 7 days of visit. All household members will receive a well-being phone call on Day 14 to continue to emphasize instructions to prevent re-infestation, determine if any concomitant medications have been used, and check for adverse events. If a subject reports an adverse event assessed as related by the PI on the Day 14 well-being phone call, then a follow-up visit with the investigator must be scheduled within 7 days of phone call.
On Day 28 (Visit 3), all household members will return to the clinic for safety and efficacy assessments. The primary endpoint of complete cure will be assessed in the "index" subject and any infested household members. If the infested subject is completely cured at Day 28, he or she will have completed the study and termination procedures will be conducted. If the subject is not completely cured at Day 28 (with Natroba™ or Placebo), the subject will receive 5% Permethrin and will be directed to their primary care physician for follow-up.
Safety assessments will be made for all household members and will include monitoring of adverse events (AEs) throughout the study, vital signs recording (Days 1 and 28), clinical laboratory analyses (Days 1 and 28), and general skin and eye irritation assessments (Days 1, 2, and 28). The Day 28 procedures will also be completed for early termination (ET) except subjects will not receive rescue Permethrin but will be directed to follow-up with their primary care physician.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Natroba (spinosad) spinosad topical suspension, 0.9% up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours |
Drug: spinosad topical suspension, 0.9%
Topically apply 0.9% suspension up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours.
Other Names:
|
| Placebo Comparator: Placebo placebo is a topical suspension that is the same formulation as Natroba without the active ingredient spinosad (vehicle). Up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours. |
Other: Placebo
Placebo is the same as the drug minus the active ingredient spinosad (vehicle). Topically apply up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours.
|
Outcome Measures
Primary Outcome Measures
- Number of Index Subjects Completely Cured of Scabies After a Single Treatment [28 days after treatment]
The primary efficacy assessment is the proportion of index subjects completely cured of scabies by Day 28. Complete cure is defined as a demonstration of both clinical cure (all signs and symptoms have completely resolved, including burrows, inflammatory/non-inflammatory lesions and pruritus) and microscopic or dermatoscopic cure demonstrating the absence of mites, eggs, and/or scybala, and a negative dermatoscopy for burrows.
Eligibility Criteria
Criteria
Inclusion Criteria:
- All household members who have provided written informed consent and an authorization for disclosure of protected health information must meet all the following criteria:
-
Male or female, age 4 years and upward.
-
At least one household member must have active scabies infestation confirmed by clinical signs and symptoms (evidence of burrows or presence of scabies inflammatory/non-inflammatory lesions and pruritus) as well as by microscopic examination of skin scraping, or dermatoscopy, to demonstrate the presence of mites, eggs, and/or scybala. If dermatoscopy is used it should also confirm there are burrows on the skin.
-
Generally in good health based on medical history and clinical assessments.
-
Normal-appearing skin in noninfested areas.
-
No history of chronic or recurrent dermatologic disease.
-
Willingness to comply with the study procedures including application of study treatment at home as instructed.
-
Willing and able to practice an acceptable measure of contraception during the study, if female of childbearing potential. Examples of acceptable contraceptive methods include abstinence, intrauterine device (IUD), double barrier method, oral or implantable or injectable contraceptives. Must have been using systemic (oral, injectable, or implantable) contraceptives for at least 3 months. If abstinent and planning to become sexually active must agree to use a double barrier method.
-
Subject agrees to inform their sexual partners to seek an examination for scabies and treatment if, and when, symptoms present.
-
Household members must be 6 or fewer and all members must be willing to attend clinic visits and be randomized to treatment (blinded, but same for all).
Exclusion Criteria:
- All household members must be excluded if any of the following conditions are met:
-
Household has greater than 6 residents.
-
Has a household member(s) who is not willing or not eligible to enroll.
-
Presence of scabies on the scalp.
-
Presence of crusted scabies (Norwegian scabies).
-
Allergies or intolerance to ingredients in the IPs.
-
Current pregnancy (as assessed by urine pregnancy test) or currently nursing.
-
The household has sexually active subjects who do not agree to restrict prolonged skin to skin contact with non-household members during the trial period.
-
Known renal or hepatic impairment.
-
Treatment with scabicide within the prior 4 weeks.
-
Immunodeficiency (including HIV infection) as reported by the subject in Medical History.
-
Signs or symptoms of systemic infection.
-
Administration of any systemic therapy for infectious disease within the prior 2 weeks.
-
Receipt of any other investigational product (IP) within the prior 4 weeks.
-
Any other conditions that, at the investigator's discretion, may interfere with the study conduct, or which might confound the interpretation of the study results, or which may put the subject at undue risk.
-
Does not have a known household affiliation with their household members (stays in one household inconsistently, i.e., sleeps at one place several nights and then other places on other nights).
-
Household member is unwilling to treat scabies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Saint Joseph's Clinical Research | Anaheim | California | United States | 92804 |
| 2 | Long Beach Clinical Trial Services | Long Beach | California | United States | 90806 |
| 3 | The Chappel Group Research | Kissimmee | Florida | United States | 34744 |
| 4 | DermDox Centers for Dermatology | Hazleton | Pennsylvania | United States | 18201 |
| 5 | Paddington Testing Company | Philadelphia | Pennsylvania | United States | 19103 |
| 6 | West Houston Clinical Research Service | Houston | Texas | United States | 77055 |
| 7 | Discovery Clinical Trials | McAllen | Texas | United States | 78503 |
Sponsors and Collaborators
- ParaPRO LLC
- Concentrics Research
Investigators
- Study Director: Kerry W Mettert, MBA, ParaPRO LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- SPN-304-15
Study Results
Participant Flow
| Recruitment Details | 18 subjects were excluded from the ITT (intent-to-treat), I-ITT (index intent-to-treat), and I-PP (index per protocol) populations due to noncompliance with the randomization procedures. As such, only 262 subjects (145 in the Natroba group and 117 in the placebo group) were included in the ITT population. |
|---|---|
| Pre-assignment Detail | Inclusion Criteria #2 - At least one household member must have active scabies infestation confirmed. |
| Arm/Group Title | Natroba (Spinosad) | Placebo |
|---|---|---|
| Arm/Group Description | spinosad topical suspension, 0.9% up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours spinosad topical suspension, 0.9%: Topically apply 0.9% suspension up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | placebo is a topical suspension that is the same formulation as Natroba without the active ingredient spinosad (vehicle). Up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours. Placebo: Placebo is the same as the drug minus the active ingredient spinosad (vehicle). Topically apply up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. |
| Period Title: Overall Study | ||
| STARTED | 154 | 126 |
| COMPLETED | 149 | 118 |
| NOT COMPLETED | 5 | 8 |
Baseline Characteristics
| Arm/Group Title | Natroba (Spinosad) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Spinosad topical suspension, 0.9% up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours Spinosad topical suspension, 0.9%: Topically apply 0.9% suspension up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | Placebo is a topical suspension that is the same formulation as Natroba without the active ingredient, spinosad (vehicle). Up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours. Placebo: Placebo is the same as the drug minus the active ingredient, spinosad (vehicle). Topically apply up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | Total of all reporting groups |
| Overall Participants | 145 | 117 | 262 |
| Age (Count of Participants) | |||
| <=18 years |
47
32.4%
|
38
32.5%
|
85
32.4%
|
| Between 18 and 65 years |
84
57.9%
|
76
65%
|
160
61.1%
|
| >=65 years |
14
9.7%
|
3
2.6%
|
17
6.5%
|
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
33.7
|
31.7
|
32.8
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
78
53.8%
|
67
57.3%
|
145
55.3%
|
| Male |
67
46.2%
|
50
42.7%
|
117
44.7%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
7
4.8%
|
7
6%
|
14
5.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
2
1.7%
|
2
0.8%
|
| Black or African American |
24
16.6%
|
14
12%
|
38
14.5%
|
| White |
112
77.2%
|
92
78.6%
|
204
77.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
1.4%
|
2
1.7%
|
4
1.5%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
145
100%
|
117
100%
|
262
100%
|
| Evidence of Burrows (Count of Participants) | |||
| Count of Participants [Participants] |
90
62.1%
|
68
58.1%
|
158
60.3%
|
| Evidence of Lesions (Count of Participants) | |||
| Count of Participants [Participants] |
103
71%
|
79
67.5%
|
182
69.5%
|
| Evidence of Pruritus (Count of Participants) | |||
| Count of Participants [Participants] |
113
77.9%
|
89
76.1%
|
202
77.1%
|
| Total Number of Pre-existing Lesions (lesions) [Mean (Full Range) ] | |||
| Mean (Full Range) [lesions] |
8.6
|
7.7
|
8.2
|
| Score of Pre-Existing Lesions (Count of Participants) | |||
| Free of Lesions |
41
28.3%
|
38
32.5%
|
79
30.2%
|
| ≤ 10 Lesions (Mild) |
48
33.1%
|
34
29.1%
|
82
31.3%
|
| 11-49 Lesions (Moderate) |
55
37.9%
|
45
38.5%
|
100
38.2%
|
| ≥ 50 Lesions (Severe) |
0
0%
|
0
0%
|
0
0%
|
| Not Done |
1
0.7%
|
0
0%
|
1
0.4%
|
| Microscopy/Dermatoscopy Result (Count of Participants) | |||
| Negative |
53
36.6%
|
48
41%
|
101
38.5%
|
| Positive |
92
63.4%
|
69
59%
|
161
61.5%
|
| Active Scabies Infestation (Count of Participants) | |||
| Count of Participants [Participants] |
92
63.4%
|
69
59%
|
161
61.5%
|
| Prior Scabies Infestation (Count of Participants) | |||
| Count of Participants [Participants] |
68
46.9%
|
68
58.1%
|
136
51.9%
|
Outcome Measures
| Title | Number of Index Subjects Completely Cured of Scabies After a Single Treatment |
|---|---|
| Description | The primary efficacy assessment is the proportion of index subjects completely cured of scabies by Day 28. Complete cure is defined as a demonstration of both clinical cure (all signs and symptoms have completely resolved, including burrows, inflammatory/non-inflammatory lesions and pruritus) and microscopic or dermatoscopic cure demonstrating the absence of mites, eggs, and/or scybala, and a negative dermatoscopy for burrows. |
| Time Frame | 28 days after treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed are based on the number of subjects who had no missing observations in each study group. |
| Arm/Group Title | Natroba (Spinosad) | Placebo |
|---|---|---|
| Arm/Group Description | spinosad topical suspension, 0.9% up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours spinosad topical suspension, 0.9%: Topically apply 0.9% suspension up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | placebo is a topical suspension that is the same formulation as Natroba without the active ingredient spinosad (vehicle). Up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours. Placebo: Placebo is the same as the drug minus the active ingredient spinosad (vehicle). Topically apply up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. |
| Measure Participants | 62 | 58 |
| Count of Participants [Participants] |
52
35.9%
|
20
17.1%
|
Adverse Events
| Time Frame | 1 year, 2 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Following randomization, 9 subjects were inaccurately dispensed Placebo instead of Natroba. Therefore, the safety population for the Natroba Arm/Group was 145 subjects (instead of the 154 randomized subjects who Started in Participant Flow) and the safety population for the Placebo Arm/Group was 135 subjects (instead of the 126 randomized subjects who Started in Participant Flow). | |||
| Arm/Group Title | Natroba (Spinosad) | Placebo | ||
| Arm/Group Description | spinosad topical suspension, 0.9% up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours spinosad topical suspension, 0.9%: Topically apply 0.9% suspension up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | placebo is a topical suspension that is the same formulation as Natroba without the active ingredient spinosad (vehicle). Up to 120 mL (enough product is used to cover the body from the neck down to the soles of the feet), one treatment left on for 6 hours. Placebo: Placebo is the same as the drug minus the active ingredient spinosad (vehicle). Topically apply up to 120 mL (enough to cover the body from the neck down to the soles of the feet). One application for six hours. | ||
All Cause Mortality |
||||
| Natroba (Spinosad) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/145 (0%) | 0/135 (0%) | ||
Serious Adverse Events |
||||
| Natroba (Spinosad) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/145 (0%) | 0/135 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Natroba (Spinosad) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/145 (2.1%) | 1/135 (0.7%) | ||
| Nervous system disorders | ||||
| Burning Sensation | 2/145 (1.4%) | 0/135 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry Skin | 1/145 (0.7%) | 0/135 (0%) | ||
| Erythema | 0/145 (0%) | 1/135 (0.7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Site may not publish or publicly present Study results. If Sponsor has given its prior written consent to the Site to publish or present Study results, Site will provide Sponsor with a copy of any proposed oral or written publication to at least sixty (60) days in advance of submission for publication or presentation for review and comment on the appropriateness of the data analysis and presentation. The terms of this paragraph shall survive expiration or termination of this Agreement.
Results Point of Contact
| Name/Title | Kerry W. Mettert, MBA, MT(ASCP) |
|---|---|
| Organization | ParaPRO, LLC |
| Phone | 317-810-6205 |
| kerrym@parapro.com |
- SPN-304-15