Dry Eye DiseasePhase 1NCT04762355
Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects
A Phase 1 study testing Palovarotene in people with Dry Eye Disease, run by Clementia Pharmaceuticals Inc. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Dry Eye Disease
- What is being tested?
- Palovarotene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteCanada
- Study dates
- 30 Aug 2018to 3 Jan 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Dry Eye Disease
- Being tested
- Palovarotene, Vehicle
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalovaroteneDrug
ophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3
VehicleDrug
Placebo-to-match palovarotene ophthalmic solution vials
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Palovarotene; Drug: Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of treatment-emergent ocular adverse events (TEAEs)
Measured: from baseline until the end of study (up to 25 days)
Change in ocular safety measurements as determined by Best-Corrected Visual Acuity (BCVA)
Measured: from baseline until the end of study (up to 25 days)
Change in Corneal Fluorescein Staining
Measured: from baseline until the end of study (up to 25 days)
Change in intraocular pressure
Measured: 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)
Measured: 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)
Measured: Day 7 and Day 10
Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t)
Measured: Day 10
Maximum observed concentration at steady state (Cmax,ss)
Measured: Day 7 and Day 10
Average concentration at steady state (Cavg)
Measured: Day 7 and Day 10
Apparent total plasma clearance after topical administration (CL/F)
Measured: Day 7 and Day 10
Time to reach Cmax at steady state (Tmax)
Measured: Day 7 and Day 10
Apparent first-order terminal elimination half-life (t½)
Measured: Day 7 and Day 10
Apparent first-order terminal elimination rate (k el)
Measured: Day 7 and Day 10
Apparent volume of distribution (Vss/F)
Measured: Day 7 and Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start30 Aug 2018
- Primary completion3 Jan 2019
- Study completion3 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dry Eye DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clementia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ipsen
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04762355
- Sponsor's protocol ID
- PVO-3A-101
- Status last verified
- Feb 2021
- First submitted
- 18 Feb 2021
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04762355
- Acronym / sponsor ID
- PVO-3A-101
- Conditions
- Dry Eye Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Clementia Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ipsen
- Study start
- 30 Aug 2018 (actual)
- Primary completion
- 3 Jan 2019 (actual)
- Study completion
- 3 Jan 2019 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose 1 | Experimental | Drug: Palovarotene, Drug: VehicleSubjects 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 |
| Dose 2 | Experimental | Drug: Palovarotene, Drug: VehicleSubjects 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 |
| Dose 3 | Experimental | Drug: Palovarotene, Drug: VehicleSubjects 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Palovaroteneophthalmic solution in different concentrations: Dose 1, Dose 2 and Dose 3 | Drug | Dose 1, Dose 2, Dose 3 |
| VehiclePlacebo-to-match palovarotene ophthalmic solution vials | Drug | Dose 1, Dose 2, Dose 3 |
Primary outcome
Number and severity of treatment-emergent ocular adverse events (TEAEs)
Time frame: 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)
Change in Corneal Fluorescein Staining
Time frame: 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)
10 secondary outcomes
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
Area under the concentration-time curve during a dosing interval (AUCtau)
Time frame: 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
Maximum observed concentration at steady state (Cmax,ss)
Time frame: Day 7 and Day 10
Average concentration at steady state (Cavg)
Time frame: Day 7 and Day 10
Apparent total plasma clearance after topical administration (CL/F)
Time frame: Day 7 and Day 10
Time to reach Cmax at steady state (Tmax)
Time frame: Day 7 and Day 10
Apparent first-order terminal elimination half-life (t½)
Time frame: Day 7 and Day 10
Apparent first-order terminal elimination rate (k el)
Time frame: Day 7 and Day 10
Apparent volume of distribution (Vss/F)
Time frame: Day 7 and Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ipsen Medical Director study director
Ipsen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Palovarotene in people with Dry Eye Disease, run by Clementia Pharmaceuticals Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and severity of treatment-emergent ocular adverse events (TEAEs) (time frame: from baseline until the end of study (up to 25 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.