A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects

• ClinicalTrials.gov Identifier: NCT03229291
• Recruitment Status: Completed
• First Posted: July 25, 2017
• Last Update Posted: July 25, 2017
• Sponsor: Biosplice Therapeutics, Inc.
• Information provided by (Responsible Party): Biosplice Therapeutics, Inc.

Study Description

Brief Summary:

This study is a single-center, randomized, single-blind, placebo-controlled, multiple ascending dose study of SM04755 solution applied topically once daily for 14 days to intact skin overlying the inner thigh of healthy subjects at an estimated body surface area (BSA) of 80 cm^2. Dosing cohorts will consist of 8 subjects who will be randomized 3:1 (SM04755:placebo).

Condition or disease	Intervention/treatment	Phase
Tendinopathy	Drug: SM04755; Drug: Vehicle	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Single-Center, Randomized, Single-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects
• Actual Study Start Date: November 3, 2016
• Actual Primary Completion Date: June 11, 2017
• Actual Study Completion Date: June 11, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose; Topical SM04755 solution (15 mg/mL) applied once per day for 14 days	Drug: SM04755; SM04755 is a small molecule inhibitor of the Wnt pathway.
Experimental: Mid Dose; Topical SM04755 solution (45 mg/mL) applied once per day for 14 days	Drug: SM04755; SM04755 is a small molecule inhibitor of the Wnt pathway.
Experimental: High Dose; Topical SM04755 solution (90 mg/mL) applied once per day for 14 days	Drug: SM04755; SM04755 is a small molecule inhibitor of the Wnt pathway.
Placebo Comparator: Vehicle; Vehicle solution applied once per day for 14 days	Drug: Vehicle; Same formulation as topical SM04755 solution, without SM04755 included.

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events (AEs) [ Time Frame: Day 28 ]
   Incidence and severity of AEs events during the treatment and observation periods of the study
2. Incidence of clinical laboratory abnormalities [ Time Frame: Day 28 ]
   Incidence and severity of clinical laboratory measurements that are outside the normal range
3. Change in vital signs: blood pressure [ Time Frame: Baseline and Day 28 ]
   Change from baseline in blood pressure
4. Change in vital signs: temperature [ Time Frame: Baseline and Day 28 ]
   Change from baseline in temperature
5. Change in vital signs: respiratory rate [ Time Frame: Baseline and Day 28 ]
   Change from baseline in respiratory rate
6. Change in vital signs: pulse rate [ Time Frame: Baseline and Day 28 ]
   Change from baseline in pulse rate
7. Change in electrocardiogram (ECG) parameters [ Time Frame: Baseline and Day 28 ]
   Change from baseline in 12-lead ECG parameters
8. Plasma pharmacokinetics (PK): Cmax [ Time Frame: Day 1 ]
   Maximum plasma concentration (Cmax) estimate for SM04755 following first dose
9. Plasma pharmacokinetics (PK):tmax [ Time Frame: Day 1 ]
   Time to Cmax estimate for SM04755 following first dose
10. Plasma pharmacokinetics (PK): AUC [ Time Frame: Day 1 ]
    Area under the plasma concentration-time curve (AUC) estimate for SM04755 following first dose
11. Plasma pharmacokinetics (PK):half-life [ Time Frame: Day 1 ]
    Plasma terminal phase half-life estimate for SM04755 following first dose
12. Plasma pharmacokinetics (PK):Cmax [ Time Frame: Day 14 ]
    Maximum plasma concentration (Cmax) estimate for SM04755 following last dose
13. Plasma pharmacokinetics (PK):tmax [ Time Frame: Day 14 ]
    Time to Cmax estimate for SM04755 following last dose
14. Plasma pharmacokinetics (PK): AUC [ Time Frame: Day 14 ]
    AUC estimate for SM04755 following last dose
15. Plasma pharmacokinetics (PK):half-life [ Time Frame: Day 14 ]
    Plasma terminal phase half-life estimate for SM04755 following last dose
16. Change in skin score assessment: erythema [ Time Frame: Baseline and Day 28 ]
    Change from baseline in erythema skin score assessment
17. Change in skin score assessment: scaling [ Time Frame: Baseline and Day 28 ]
    Change from baseline in scaling skin score assessment
18. Change in skin score assessment: pruritus/itching [ Time Frame: Baseline and Day 28 ]
    Change from baseline in pruritus/itching skin score assessment
19. Change in skin score assessment: burning/stinging [ Time Frame: Baseline and Day 28 ]
    Change from baseline in burning/stinging skin score assessment

Secondary Outcome Measures :

1. Incidence of AEs relative to exposure [ Time Frame: Day 28 ]
   Incidence and severity of AEs relative to measured plasma exposure to SM04755

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Body mass index of 18 to 30 kg/m^2 at study start
• Subject must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed
• Willingness to comply with all scheduled study visits, laboratory tests, contraception requirements and other study procedures
• Appropriate skin characteristics at site of application (inner thigh) (for example, consistent pigmentation, no tattoos, no scarring or noted injury, no varicose veins or structural repair)
• Willing to avoid extensive sun exposure, phototherapy, or use of a tanning salon for the duration of the study

Exclusion Criteria:

• Women who are pregnant or lactating
• Women of childbearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period that includes double barrier, intrauterine device (IUD), or hormonal contraceptive combined with single barrier, or abstinence
• Males who are sexually active and not willing to use a condom, and have a partner who is capable of becoming pregnant, if neither has had surgery to become sterilized, and/or who are not willing to use double barrier or whose partner is not using a highly effective method of birth control (e.g., IUD or hormonal contraception combined with single barrier).
• History of, or current, skin disease (for example, psoriasis, atopic dermatitis, seborrheic dermatitis, and skin cancer)
• History of, or current, skin damage at the treatment site (inner thigh) (for example, cuts, abrasion, sunburn, sun-damage, or scarring)
• Phototherapy or use of a tanning salon 2 weeks prior to study start until end of the study (Day 28)
• History of, or current, allergy to investigational product/placebo ingredients
• Known allergy to adhesive tape
• Current evidence of malignancy or history of malignancy within the last 5 years prior to study start; prior history of in situ cancer or basal or squamous cell skin cancer, completely excised, is allowed
• Treatment with an investigational product within 12 weeks prior to study start; the last date of participation in the trial, not the last date of receipt of investigational product, must be at least 12 weeks prior to study start
• Use of any prescription or nonprescription drugs [except birth control or hormone replacement therapy (HRT)], topical skin treatments on the application site (inner thigh), vitamins, grapefruit/grapefruit juice, or dietary or herbal supplements within 14 days prior to study start
• Blood donation of ≥ 1 pint (473 mL) within 56 days prior to study start or unwilling to refrain from blood donation for the duration of the study
• Plasma or platelet donation within 14 days prior to study start or unwilling to refrain from plasma or platelet donation for the duration of the study
• Unwilling to refrain from sperm donation for the duration of the study and until 90 days after dose administration
• Prior or current latent or active tuberculosis (TB) or nontuberculous mycobacteria infection.
• Evidence of active infection or illness involving fever within 7 days prior to study start
• Occurrence of serious illness requiring hospitalization within 6 months prior to study start
• Regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months prior to study start
• Use of tobacco- or nicotine-containing products (cigarettes, pipe, cigar, chewing tobacco or nicotine gum, lozenges or patches) within 30 days prior to study start
• A history of abuse of prescription or illicit drugs within 6 months prior to study start
• Marijuana use within 28 days prior to study start
• Previous treatment with SM04755
• Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
• Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site
• Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study

Contacts and Locations

Locations

United States, Arizona

Research Site

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

Biosplice Therapeutics, Inc.

Investigators

• Study Director: Yusuf Yazici, M.D.; Biosplice Therapeutics, Inc.

More Information

• Responsible Party: Biosplice Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03229291
• Other Study ID Numbers: SM04755-TOP-01
• First Posted: July 25, 2017
• Last Update Posted: July 25, 2017
• Last Verified: July 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biosplice Therapeutics, Inc.:

SM04755; topical; Samumed; Wnt inhibitor

Additional relevant MeSH terms:

Tendinopathy; Muscular Diseases; Musculoskeletal Diseases; Tendon Injuries; Wounds and Injuries