E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peri-Implantitis, defined as a condition around an osseointegrated dental implant having at least one peri-implant site with probing depth (PD) ≥5 mm and ≤7 mm that exhibits bleeding on probing and displays radiographic evidence of peri-implant bone loss. The condition is typically accompanied by an underlying bacterial infection. |
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E.1.1.1 | Medical condition in easily understood language |
An inflammatory process caused by a bacterial infection, affecting the tissues around an implant already integrated into the bone. The inflamation results in loss of supporting bone around the implant |
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E.1.1.2 | Therapeutic area | Diseases [C] - Mouth and tooth diseases [C07] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of a locally delivered antibiotic, Minocycline HCl Microspheres, 1 mg, for the treatment of peri-implantitis, when used as an adjunct to mechanical debridement. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- At least 21 years of age and in good general health. - Subjects (and/or their legally acceptable representatives) must have read and signed an informed consent form indicating that they fully understand the purpose and procedures required for the study and are willing to participate in the study. Each subject will receive a copy of his/her signed informed consent document. - Willing to adhere to the study schedule, prohibitions and restrictions specified in the protocol. - Male subjects who are not surgically sterilized must be practicing an effective method of birth control for the duration of the study. - Female subjects of childbearing potential must be practicing an effective method of birth control. - Must be free from any significant oral soft tissue pathology - Must have a minimum of one* (1) osseointegrated (e.g., endosteal root form/cylindrical) implant with a diagnosis of peri-implantitis - Must have at least one peri-implant site with an average of two PD readings ≥5 to ≤7 mm when using a light force, with BOP within 30 seconds of the probing and evidence of pathologic bone loss. Peri-implant bone loss will be confirmed by a dentist (Investigator, treating clinician or examiner) through the use of a recent (6 months or less) radiograph (a panoramic film is acceptable). If a recent radiograph is not available, a radiograph (e.g. periapical) will be taken at the Screening visit. Evidence of bone loss could be present anywhere around the implant. The bone loss is not required to be around the circumference of the implant, nor at the specific location of the qualifying site(s) (pocket(s)) of the implant. - At least 1mm of keratinized gingiva must be present anywhere around the implant. The keratinized gingiva is not required to be around the circumference of the implant nor at the specific location of the qualifying site(s) (pocket(s)) of the implant.
*Note: the single osseointegrated implant can be a single implant, or an implant bearing a fixed partial denture (i.e., fixed bridge) or full removable denture or overdenture. Fixed overdentures may be included if the examiner has full access to accurately probe and assess the study implant(s). |
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E.4 | Principal exclusion criteria |
- Females having a positive urine pregnancy result at the time of randomization - Male subjects reporting pregnancy or lactation of their partner. - Subjects reporting allergy to a tetracycline-class drug. - Subjects with any systemic medical conditions requiring antibiotic prophylaxis prior to invasive dental procedures. - Subjects with any active systemic infectious disease such as hepatitis, human immunodeficiency virus (HIV) or history of tuberculosis - Subjects diagnosed with clinically significant or unstable organic disease(e.g., severely impaired liver function or acute or chronic end stage renal failure), or compromised healing potential - Subjects taking antibiotics or other medication as described in Section 8.7 of the protocol - Subjects who have taken any investigational drug within 30 days of enrollment - Subjects who have participated in a dental clinical trial within 30 days of enrollment - Employees of the Investigator or study center, with direct involvement in the proposed study or other studies, as well as family members of the employees or the Investigator - Any subject that at the discretion of the Investigator should not be included in the study due to anticipated poor compliance with study visits (e.g., transportation challenges or personal issues) - Subjects presenting with signs of untreated advanced periodontal disease and/or poor oral hygiene - Subjects having an average of 2 PD >7mm at any peri-implant site(s) at time of enrollment - Subjects presenting with mobility of any dental implant - Subjects having a qualifying implant under occlusal trauma or overloaded, as determined by the Investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in average probing depth of qualifying implant sites from baseline to Day 180. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The analysis will be performed at day 180 from baseline visit. |
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E.5.2 | Secondary end point(s) |
-Change in percentage of qualifying implants with Bleeding on Probing (BOP) at Day 180 -Change in average probing depth if qualifying implant sites at Day 90
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Change from baseline to Day 180 in percentage of qualifying implants with BOP -Change from baseline to Day 90 in mean probing depth for qualifying implant sites -Change from baseline to Day 90 in percentage of qualifying implants with BOP
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Examining clinician at study center will be blinded to patient treatment assignments. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No adjunct medical therapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |