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Long-term Safety of Minocycline in Patients With Gum Disease

Sponsor
OraPharma (Industry)
Overall Status
Completed
CT.gov ID
NCT00668746
Collaborator
(none)
35
Enrollment
1
Location
2
Arms
14.1
Duration (Months)
2.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will look at the safety of using the study medicine for a long time. It will see if the germs get used to the medicine, making it not work as well, if it's used by people with gum disease for a long time.

Condition or Disease Intervention/Treatment Phase
  • Drug: Minocycline HCl microspheres
 Phase 4

Detailed Description

The objective of this study is to evaluate the changes in populations of minocycline-resistant bacteria after long-term use of minocycline HCl microspheres, 1 mg in subjects with moderate-to-severe chronic periodontitis. This will be assessed through monitoring the total number and proportion of minocycline-resistant bacteria and the identity of minocycline-resistant species within a panel of 40 representative periodontal species in saliva and subgingival plaque.

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Long-term Safety Evaluation of Minocycline Resistance After Treatment With Minocycline HCl Microspheres, 1 mg in Subjects With Chronic Periodontitis
Study Start Date :
Dec 1, 2007
Actual Primary Completion Date :
Feb 1, 2009
Actual Study Completion Date :
Feb 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Minocycline HCl microspheres

Minocycline HCl microspheres

Drug: Minocycline HCl microspheres
At Baseline and all interim visits, a single unit dose of 1mg minocycline HCl (with approximately 3mg PGLA) will be professionally administered subgingivally into periodontal pockets at each site exhibiting a PD ≥ 5mm.
Other Names:
  • minocycline

    		•
    No Intervention: No drug intervention

    No drug intervention

    Outcome Measures

    Primary Outcome Measures

    1. Change in Percent of Minocycline-Resistant Bacteria Using Bacterial Culture [from Baseline to Day 30 and Day 180]

      Percentage Change from Baseline is calculated as post-baseline percent minus baseline percent.

    Secondary Outcome Measures

    1. Micocycline-Resistance From Plaque Samples [Baseline, Day 30 and Day 180]

      Percentage of Subjects showing Micocycline-Resistance for each Species from Plaque Samples DNA Method: Plaque Sample Intent-to-Treat Subjects - we report average of percentage for 4 plaque samples

    2. Micocycline-Resistance From Saliva Sample [Baseline, Day 30 and Day 180]

      Percentage of Subjects Showing Micocycline-Resistance for each Species from Saliva Sample DNA Method: Saliva Sample Intent-to-treat Subjects

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • generally healthy

    • over 25 years of age

    • moderate-to-severe chronic periodontitis

    • documented informed consent

    • willing to comply with contraceptive requirements

    • free from any significant oral soft tissue pathology

    Exclusion Criteria:

    • willing to adhere to prohibitions and restrictions of the study

    • oral health inappropriate for study inclusion

    • females self-reporting pregnancy or lactation, or having a positive urine pregnancy result

    • reporting any of the following conditions:

    • allergy to a tetracycline-class drug

    • systemic medical conditions requiring antibiotic prophylaxis prior to invasive dental procedures

    • active systemic infectious disease such as hepatitis, human immunodeficiency virus (HIV) or tuberculosis

    • diagnosed with clinically significant or unstable organic disease, or compromised healing potential, heart murmurs, histories of rheumatic fever, valvular disease or prosthetic joint replacement

    • participation in a dental clinical trial or use of an investigational drug 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

    • anyone who the investigator determines should not be included in the study for any reason that could compromise safety or the analysis of study results

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Forsyth Institute Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • OraPharma

    Investigators

    • Study Director: Michael Lynch, DMD, PhD, OraPharma

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    OraPharma
    ClinicalTrials.gov Identifier:
    NCT00668746
    Other Study ID Numbers:
    • OP-P-5756-1
    First Posted:
    Apr 29, 2008
    Last Update Posted:
    Dec 12, 2011
    Last Verified:
    Dec 1, 2011
    Keywords provided by OraPharma
    chronic periodontitis, antibiotic resistance
    Additional relevant MeSH terms:
    Periodontitis
    Chronic Periodontitis
    Minocycline

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Minocycline HCl Microspheres No Drug Intervention
    Arm/Group Description A single unit dose of 1mg minocycline HCl (with approximately 3mg PGLA) professionally administered subgingivally into periodontal pockets at each site exhibiting a PD ≥ 5mm A control consisting of no drug intervention
    Period Title: Overall Study
    STARTED 23 12
    COMPLETED 21 11
    NOT COMPLETED 2 1

    Baseline Characteristics

    Arm/Group Title Minocycline HCl Microspheres No Drug Intervention Total
    Arm/Group Description A single unit dose of 1mg minocycline HCl (with approximately 3mg PGLA) professionally administered subgingivally into periodontal pockets at each site exhibiting a PD ≥ 5mm A control consisting of no drug intervention Total of all reporting groups
    Overall Participants 23 12 35
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.65
    (10.71)
    52.83
    (9.90)
    56.00
    (10.55)
    Sex: Female, Male (Count of Participants)
    Female
    9
    39.1%
    2
    16.7%
    11
    31.4%
    Male
    14
    60.9%
    10
    83.3%
    24
    68.6%
    Region of Enrollment (participants) [Number]
    United States
    23
    100%
    12
    100%
    35
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Percent of Minocycline-Resistant Bacteria Using Bacterial Culture
    Description Percentage Change from Baseline is calculated as post-baseline percent minus baseline percent.
    Time Frame from Baseline to Day 30 and Day 180

    Outcome Measure Data

    Analysis Population Description
    intention to treat (ITT)
    Arm/Group Title Minocycline HCl Microspheres No Drug Intervention
    Arm/Group Description A single unit dose of 1mg minocycline HCl (with approximately 3mg PGLA) professionally administered subgingivally into periodontal pockets at each site exhibiting a PD ≥ 5mm A control consisting of no drug intervention
    Measure Participants 23 12
    Plaque Sample at Day 30
    13.15
    (19.77)
    0.81
    (3.33)
    Saliva Sample at Day 30
    37.65
    (113.9)
    -2.25
    (6.18)
    Plaque Sample at Day 180
    8.09
    (19.77)
    1.58
    (2.49)
    Saliva Sample at Day 180
    12.06
    (18.35)
    -0.51
    (10.70)
    2. Secondary Outcome
    Title Micocycline-Resistance From Plaque Samples
    Description Percentage of Subjects showing Micocycline-Resistance for each Species from Plaque Samples DNA Method: Plaque Sample Intent-to-Treat Subjects - we report average of percentage for 4 plaque samples
    Time Frame Baseline, Day 30 and Day 180

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title Minocycline Group at Baseline Minocycline Group at 30 Days Micocycline Group at 180 Days Control Group at Baseline Control Group at 30 Days Control Group at 180 Days
    Arm/Group Description
    Measure Participants 23 23 23 12 12 12
    A.naeslundii
    7.14
    1.19
    17.86
    6.82
    6.82
    13.64
    S.constellatus
    65.48
    67.86
    73.81
    79.55
    70.45
    81.82
    E.nodatum
    3.57
    3.57
    13.10
    11.36
    6.82
    13.64
    P.gingivalis
    29.76
    21.43
    7.14
    29.55
    15.91
    2.27
    A.actinomucetemcomitans
    7.14
    16.67
    19.05
    22.73
    25.00
    11.36
    F.nucleatum vincentii
    7.14
    11.90
    9.52
    9.09
    9.09
    9.09
    C.rectus
    9.52
    13.10
    11.90
    22.73
    13.64
    11.36
    R.dentocariosa
    0.00
    2.38
    5.95
    9.09
    9.09
    2.27
    E.saburreum
    16.67
    16.67
    65.48
    25.00
    18.18
    65.91
    P.micra
    8.33
    15.48
    23.81
    29.55
    22.73
    9.09
    V.parvula
    41.67
    71.43
    53.57
    47.73
    54.55
    31.82
    A.oris
    19.05
    13.10
    7.14
    25.00
    20.45
    2.27
    S.anginosus
    30.95
    30.95
    34.52
    50.00
    59.09
    50.00
    S.anguinis
    76.19
    85.71
    88.10
    75.00
    77.27
    90.91
    A.gerencseriae
    3.57
    10.71
    2.38
    6.82
    6.82
    0.00
    S.oralis
    70.24
    78.57
    82.14
    77.27
    79.55
    88.64
    C.ochraccea
    1.19
    0.00
    1.19
    2.27
    0.00
    0.00
    A.israelli
    0.00
    2.38
    2.38
    2.27
    0.00
    0.00
    S.intermedius
    48.81
    65.48
    76.19
    63.64
    63.64
    81.82
    C.matruchotti
    2.38
    3.57
    8.33
    4.55
    6.82
    0.00
    P.nigrescens
    5.95
    8.33
    3.57
    11.36
    2.27
    9.09
    A.odontolyticus
    4.76
    19.05
    21.43
    25.00
    20.45
    9.09
    F.nucleatum polymorphum
    11.90
    25.00
    16.67
    13.64
    15.91
    13.64
    C.showae
    4.76
    10.71
    7.14
    34.09
    15.91
    15.91
    F.periodonticum
    1.19
    9.52
    2.38
    2.27
    0.00
    0.00
    N.mucosa
    35.71
    27.38
    58.33
    36.36
    36.36
    61.36
    F.nucleatum
    1.19
    3.57
    0.00
    0.00
    0.00
    0.00
    C.ginigivaluis
    15.48
    17.86
    7.14
    20.45
    15.91
    2.27
    S.gordonii
    72.62
    91.67
    69.05
    81.82
    75.00
    77.27
    T.forsythia
    1.19
    2.38
    0.00
    0.00
    0.00
    2.27
    S.noxia
    51.19
    65.48
    55.95
    65.91
    54.55
    50.00
    P.acnes
    1.19
    8.33
    10.71
    9.09
    11.36
    11.36
    P.melaninogenica
    7.14
    3.57
    2.38
    2.27
    2.27
    13.64
    S.mitis
    75.00
    79.76
    75.00
    81.82
    77.27
    90.91
    E.corrodens
    53.57
    57.14
    42.86
    65.91
    52.27
    25.00
    G.morbillorum
    22.62
    22.62
    78.57
    36.36
    22.73
    88.64
    C.sputigena
    1.19
    0.00
    3.57
    4.55
    0.00
    4.55
    L.bucallis
    34.52
    21.43
    28.57
    29.55
    20.45
    15.91
    C.gracilis
    7.14
    4.76
    4.76
    4.55
    0.00
    0.00
    P.intermedia
    29.76
    19.05
    36.90
    27.27
    18.18
    31.82
    3. Secondary Outcome
    Title Micocycline-Resistance From Saliva Sample
    Description Percentage of Subjects Showing Micocycline-Resistance for each Species from Saliva Sample DNA Method: Saliva Sample Intent-to-treat Subjects
    Time Frame Baseline, Day 30 and Day 180

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title Minocycline Group at Baseline Minocycline Group at Day 30 Minocycline Group at Day 180 Control Group at Baseline Control Group at Day 30 Control Group at Day 180
    Arm/Group Description
    Measure Participants 23 23 23 12 12 12
    A.naeslundii
    4.76
    0.00
    19.05
    9.09
    9.09
    0.00
    S.constellatus
    47.62
    42.86
    80.95
    72.73
    63.64
    63.64
    E.nodatum
    4.76
    0.00
    14.29
    9.09
    0.00
    9.09
    P.gingivalis
    23.81
    19.05
    9.52
    27.27
    18.18
    18.18
    A.actinomucetemcomitans
    19.05
    9.52
    14.29
    27.27
    0.00
    27.27
    F.nucleatum vincentii
    9.52
    0.00
    19.05
    9.09
    0.00
    18.18
    C.rectus
    9.52
    9.52
    14.29
    18.18
    0.00
    0.00
    R.dentocariosa
    4.76
    0.00
    14.29
    9.09
    0.00
    9.09
    E.saburreum
    19.05
    14.29
    61.90
    27.27
    0.00
    72.73
    P.micra
    14.29
    9.52
    23.81
    18.18
    0.00
    18.18
    V.parvula
    61.90
    90.48
    80.95
    81.82
    81.82
    90.91
    A.oris
    14.29
    14.29
    14.29
    27.27
    18.18
    9.09
    S.anginosus
    14.29
    14.29
    42.86
    27.27
    9.09
    45.45
    S.anguinis
    61.90
    85.71
    100.00
    72.73
    72.73
    100.00
    A.gerencseriae
    4.76
    14.29
    9.52
    9.09
    0.00
    9.09
    S.oralis
    66.67
    71.43
    100.00
    63.64
    90.91
    90.91
    C.ochraccea
    0.00
    0.00
    4.76
    9.09
    0.00
    0.00
    A.israelli
    0.00
    0.00
    0.00
    9.09
    0.00
    0.00
    S.intermedius
    42.86
    38.10
    80.95
    63.64
    45.45
    90.91
    C.matruchotti
    9.52
    9.52
    23.81
    9.09
    9.09
    36.36
    P.nigrescens
    9.52
    4.76
    0.00
    0.00
    0.00
    0.00
    A.odontolyticus
    23.81
    19.05
    28.57
    45.45
    0.00
    36.36
    F.nucleatum polymorphum
    19.05
    19.05
    14.29
    9.09
    9.09
    27.27
    C.showae
    19.05
    9.52
    4.76
    36.36
    0.00
    9.09
    F.periodonticum
    4.76
    4.76
    4.76
    9.09
    0.00
    0.00
    N.mucosa
    47.62
    28.57
    76.19
    36.36
    27.27
    72.73
    F.nucleatum
    0.00
    0.00
    9.52
    0.00
    0.00
    9.09
    C.ginigivaluis
    23.81
    9.52
    19.05
    18.18
    0.00
    9.09
    S.gordonii
    71.43
    85.71
    66.67
    72.73
    45.45
    72.73
    T.forsythia
    0.00
    0.00
    0.00
    0.00
    0.00
    0.00
    S.noxia
    52.38
    52.38
    57.14
    54.55
    54.55
    72.73
    P.acnes
    9.52
    9.52
    19.05
    9.09
    0.00
    27.27
    P.melaninogenica
    0.00
    0.00
    19.05
    18.18
    18.18
    0.00
    S.mitis
    61.90
    71.43
    90.48
    81.82
    90.91
    100.00
    E.corrodens
    57.14
    47.62
    57.14
    72.73
    81.82
    45.45
    G.morbillorum
    38.10
    14.29
    76.19
    27.27
    0.00
    100.00
    C.sputigena
    9.52
    4.76
    0.00
    9.09
    0.00
    0.00
    L.bucallis
    33.33
    23.81
    38.10
    18.18
    9.09
    27.27
    C.gracilis
    0.00
    0.00
    4.76
    0.00
    0.00
    0.00
    P.intermedia
    23.81
    19.05
    33.33
    18.18
    27.27
    54.55

    Adverse Events

    Time Frame 180 Days
    Adverse Event Reporting Description
    Arm/Group Title Minocycline HCl Microspheres No Drug Intervention
    Arm/Group Description A single unit dose of 1mg minocycline HCl (with approximately 3mg PGLA) professionally administered subgingivally into periodontal pockets at each site exhibiting a PD ≥ 5mm A control consisting of no drug intervention
    All Cause Mortality
    Minocycline HCl Microspheres No Drug Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Minocycline HCl Microspheres No Drug Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/23 (4.3%) 1/12 (8.3%)
    Cardiac disorders
    Myocardial infarction 1/23 (4.3%) 1 0/12 (0%) 0
    Gastrointestinal disorders
    Intestinal Obstruction 0/23 (0%) 0 1/12 (8.3%) 1
    Other (Not Including Serious) Adverse Events
    Minocycline HCl Microspheres No Drug Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/23 (34.8%) 7/12 (58.3%)
    Gastrointestinal disorders
    ORAL DISCOMFORT 0/23 (0%) 0 1/12 (8.3%) 1
    TOOTHACHE 2/23 (8.7%) 2 0/12 (0%) 0
    INTESTINAL OBSTRUCTION 0/23 (0%) 0 1/12 (8.3%) 1
    Infections and infestations
    SINUSITIS 2/23 (8.7%) 2 0/12 (0%) 0
    ABSCESS ORAL 0/23 (0%) 0 1/12 (8.3%) 1
    Injury, poisoning and procedural complications
    TOOTH FRACTURE 2/23 (8.7%) 2 0/12 (0%) 0
    Investigations
    BLOOD GLUCOSE INCREASED 0/23 (0%) 0 1/12 (8.3%) 1
    Musculoskeletal and connective tissue disorders
    BACK PAIN 0/23 (0%) 0 1/12 (8.3%) 1
    PAIN IN EXTREMITY 2/23 (8.7%) 2 0/12 (0%) 0
    Surgical and medical procedures
    TOOTH EXTRACTION 0/23 (0%) 0 1/12 (8.3%) 1
    Vascular disorders
    HYPERTENSION 0/23 (0%) 0 1/12 (8.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Ms. Bindu Patel, Senior Scientist, Regulatory Affairs and Quality Assurance
    Organization OraPharma
    Phone 215-420-4064
    Email bpatel@orapharma.com
    Responsible Party:
    OraPharma
    ClinicalTrials.gov Identifier:
    NCT00668746
    Other Study ID Numbers:
    • OP-P-5756-1
    First Posted:
    Apr 29, 2008
    Last Update Posted:
    Dec 12, 2011
    Last Verified:
    Dec 1, 2011