Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects

NCT04762355 | Completed Phase 1 DMC

• 1 other identifier: PVO-3A-101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Dry eye disease (DED) is a keratoconjunctive disorder that "is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. The goal of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses of palovarotene ophthalmic solution in healthy adult subjects.

Conditions

Dry Eye Disease

Outcome Measures

Primary Outcomes (4)

• Number and severity of treatment-emergent ocular adverse events (TEAEs)

  from baseline until the end of study (up to 25 days)

• Change in ocular safety measurements as determined by Best-Corrected Visual Acuity (BCVA)

  from baseline until the end of study (up to 25 days)

• Change in Corneal Fluorescein Staining

  from baseline until the end of study (up to 25 days)

• Change in intraocular pressure

  from baseline until the end of study (up to 25 days)

Secondary Outcomes (10)

• Plasma concentration (predose) observed at the end of a dosing interval (Ctrough)

  Day 5 and Day 6 (prior to the morning), Day 7 ((prior to the morning), Day 8, Day 9, Day 10

• Area under the concentration-time curve during a dosing interval (AUCtau)

  Day 7 and Day 10

• Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t)

  Day 10

• Maximum observed concentration at steady state (Cmax,ss)

  Day 7 and Day 10

• Average concentration at steady state (Cavg)

  Day 7 and Day 10

Study Arms (3)

Dose 1

EXPERIMENTAL

Subjects were randomized in a 3:1 ratio to receive one dose regimen of either active treatment or placebo (vehicle). Advancement of the study from the once daily (QD) dosing regimen to the twice daily (BID) dosing regimen, and dose escalation to the next dose regimen

Drug: Palovarotene; Drug: Vehicle

Dose 2

EXPERIMENTAL

Subjects were randomized in a 3:1 ratio to receive one dose regimen of either active treatment or placebo (vehicle). Advancement of the study from the once daily (QD) dosing regimen to the twice daily (BID) dosing regimen, and dose escalation to the next dose regimen

Drug: Palovarotene; Drug: Vehicle

Dose 3

EXPERIMENTAL

Subjects were randomized in a 3:1 ratio to receive one dose regimen of either active treatment or placebo (vehicle). Advancement of the study from the once daily (QD) dosing regimen to the twice daily (BID) dosing regimen, and dose escalation to the next dose regimen

Drug: Palovarotene; Drug: Vehicle

Interventions

Palovarotene DRUG

ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3

Dose 1; Dose 2; Dose 3

Vehicle DRUG

Placebo-to-match palovarotene ophthalmic solution vials

Dose 1; Dose 2; Dose 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female, 18 to 55 years of age, inclusive, at screening.
• Continuous non-smoker who had not used nicotine containing products for at least 3 months prior to the first dosing and throughout the study, based on subject self-reporting.
• Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2 at screening.
• Medically healthy as deemed by the Investigator or delegate and determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical laboratory results obtained within 28 days before the start of the study.
• Tolerate topical administration to the eye.
• Best corrected visual acuity is equal or better than 70 Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in both eyes.

You may not qualify if:

• Mentally or legally incapacitated or had significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical (systemic or ophthalmic) or psychiatric condition or disease in the opinion of the Investigator or delegate.
• History of any illness that, in the opinion of the Investigator or delegate, might have confounded the results of the study or posed an additional risk to the subject by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 18 months prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug, systemic retinoids such as isotretinoin or related compounds (e.g., topical tretinoins, vitamin A), fluorescein, or parabens or to the inactive ingredients in the study formulation.
• History of any ocular surgery or laser within the past 6 months prior to screening.
• History of herpes simplex keratitis.
• History or presence of:
• Any chronic eye disease other than refractive error, incipient cataract, strabismic amblyopia, or anisometropic amblyopia.
• Acute eye disease (such as infection, corneal abrasion, or allergy) within the past 6 months from screening.
• Any currently active ocular condition that required use of topical eye drops.
• Had an intraocular pressure \>21 mmHg.
• If ophthalmological examination at screening or Day 1 predose revealed abnormalities of the cornea, evidence of ocular infection, inflammation (dry eyes, blepharitis, allergic conjunctivitis, iritis, and uveitis), advanced or moderately injected pterygium, keratitis, narrow anterior chamber angles, clinically significant Meibomian gland dysfunction, or any finding in either the anterior segment or posterior segment of the eye, that could have compromised the study as per Investigator or delegate discretion.
• Any macular integrity issues or optic nerve head (ONH) cupping/abnormality on retinal exam.
• Occurrence of active seasonal allergies including ocular allergies (e.g., annual hay fever).

Sponsors & Collaborators

• Clementia Pharmaceuticals Inc.: lead
• Ipsen: collaborator

Study Sites (1)

Algorithme Pharma facility

Québec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

Palovarotene

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 21, 2021
• Study Start: August 30, 2018
• Primary Completion: January 3, 2019
• Study Completion: January 3, 2019
• Last Updated: February 21, 2021

Record last verified: 2021-02

Locations

CA (1)