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

NCT03229291 | Completed Phase 1 FDA Drug

• 1 other identifier: SM04755-TOP-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Tendinopathy

Keywords

SM04755; topical; Samumed; Wnt inhibitor

Outcome Measures

Primary Outcomes (19)

• Incidence of adverse events (AEs)

  Incidence and severity of AEs events during the treatment and observation periods of the study

  Day 28

• Incidence of clinical laboratory abnormalities

  Incidence and severity of clinical laboratory measurements that are outside the normal range

  Day 28

• Change in vital signs: blood pressure

  Change from baseline in blood pressure

  Baseline and Day 28

• Change in vital signs: temperature

  Change from baseline in temperature

  Baseline and Day 28

• Change in vital signs: respiratory rate

  Change from baseline in respiratory rate

  Baseline and Day 28

• Change in vital signs: pulse rate

  Change from baseline in pulse rate

  Baseline and Day 28

• Change in electrocardiogram (ECG) parameters

  Change from baseline in 12-lead ECG parameters

  Baseline and Day 28

• Plasma pharmacokinetics (PK): Cmax

  Maximum plasma concentration (Cmax) estimate for SM04755 following first dose

  Day 1

• Plasma pharmacokinetics (PK):tmax

  Time to Cmax estimate for SM04755 following first dose

  Day 1

• Plasma pharmacokinetics (PK): AUC

  Area under the plasma concentration-time curve (AUC) estimate for SM04755 following first dose

  Day 1

• Plasma pharmacokinetics (PK):half-life

  Plasma terminal phase half-life estimate for SM04755 following first dose

  Day 1

• Plasma pharmacokinetics (PK):Cmax

  Maximum plasma concentration (Cmax) estimate for SM04755 following last dose

  Day 14

• Plasma pharmacokinetics (PK):tmax

  Time to Cmax estimate for SM04755 following last dose

  Day 14

• Plasma pharmacokinetics (PK): AUC

  AUC estimate for SM04755 following last dose

  Day 14

• Plasma pharmacokinetics (PK):half-life

  Plasma terminal phase half-life estimate for SM04755 following last dose

  Day 14

• Change in skin score assessment: erythema

  Change from baseline in erythema skin score assessment

  Baseline and Day 28

• Change in skin score assessment: scaling

  Change from baseline in scaling skin score assessment

  Baseline and Day 28

• Change in skin score assessment: pruritus/itching

  Change from baseline in pruritus/itching skin score assessment

  Baseline and Day 28

• Change in skin score assessment: burning/stinging

  Change from baseline in burning/stinging skin score assessment

  Baseline and Day 28

Secondary Outcomes (1)

• Incidence of AEs relative to exposure

  Day 28

Study Arms (4)

Low Dose

EXPERIMENTAL

Topical SM04755 solution (15 mg/mL) applied once per day for 14 days

Drug: SM04755

Mid Dose

EXPERIMENTAL

Topical SM04755 solution (45 mg/mL) applied once per day for 14 days

Drug: SM04755

High Dose

EXPERIMENTAL

Topical SM04755 solution (90 mg/mL) applied once per day for 14 days

Drug: SM04755

Vehicle

PLACEBO COMPARATOR

Vehicle solution applied once per day for 14 days

Drug: Vehicle

Interventions

SM04755 DRUG

SM04755 is a small molecule inhibitor of the Wnt pathway.

High Dose; Low Dose; Mid Dose

Vehicle DRUG

Same formulation as topical SM04755 solution, without SM04755 included.

Vehicle

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (1)

Research Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Conditions

Tendinopathy

Condition Hierarchy (Ancestors)

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

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 25, 2017
• Study Start: November 3, 2016
• Primary Completion: June 11, 2017
• Study Completion: June 11, 2017
• Last Updated: July 25, 2017

Record last verified: 2017-07

Locations

US (1)