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

February 18, 2021 updated by: Clementia Pharmaceuticals Inc.

A Phase 1, Double-Masked, Vehicle-Controlled Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Québec, Canada, H3P 3P1
        • Algorithme Pharma facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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:

    1. Any chronic eye disease other than refractive error, incipient cataract, strabismic amblyopia, or anisometropic amblyopia.
    2. 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).
  • Needed to wear contact lenses during the study.
  • Positive results at screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus.
  • Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing and throughout the study, unless permitted by the Investigator or delegate.
  • Any drugs known to be significant inhibitors and inducers of CYP3A4 enzymes, including St. John's Wort, for 30 days prior to the first dosing and throughout the study.
  • Ocular medication of any kind (including artificial tears), antihistamines, anticholinergics, and/or oral/nasal steroids for 30 days prior to the first dosing and throughout the study.
  • Isotretinoin or other systemic retinoids beginning 30 days or 5 half-lives, whichever was longer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose 1
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
ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3
Drug: Vehicle
Placebo-to-match palovarotene ophthalmic solution vials
Experimental: Dose 2
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
ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3
Drug: Vehicle
Placebo-to-match palovarotene ophthalmic solution vials
Experimental: Dose 3
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
ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3
Drug: Vehicle
Placebo-to-match palovarotene ophthalmic solution vials

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number and severity of treatment-emergent ocular adverse events (TEAEs)
Time Frame: from baseline until the end of study (up to 25 days)
from baseline until the end of study (up to 25 days)
Change in ocular safety measurements as determined by Best-Corrected Visual Acuity (BCVA)
Time Frame: from baseline until the end of study (up to 25 days)
from baseline until the end of study (up to 25 days)
Change in Corneal Fluorescein Staining
Time Frame: from baseline until the end of study (up to 25 days)
from baseline until the end of study (up to 25 days)
Change in intraocular pressure
Time Frame: from baseline until the end of study (up to 25 days)
from baseline until the end of study (up to 25 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Plasma concentration (predose) observed at the end of a dosing interval (Ctrough)
Time Frame: Day 5 and Day 6 (prior to the morning), Day 7 ((prior to the morning), Day 8, Day 9, Day 10
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)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t)
Time Frame: Day 10
Day 10
Maximum observed concentration at steady state (Cmax,ss)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Average concentration at steady state (Cavg)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Apparent total plasma clearance after topical administration (CL/F)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Time to reach Cmax at steady state (Tmax)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Apparent first-order terminal elimination half-life (t½)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Apparent first-order terminal elimination rate (k el)
Time Frame: Day 7 and Day 10
Day 7 and Day 10
Apparent volume of distribution (Vss/F)
Time Frame: Day 7 and Day 10
Day 7 and Day 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Clementia Pharmaceuticals Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ipsen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 3, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 3, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PVO-3A-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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