CTRI/2023/03/051072 [Registered on: 27/03/2023] Trial Registered Prospectively
Last Modified On:
24/01/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Dentistry
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Effect of Doxycycline and Metformin Gel in Periodontitis
Scientific Title of Study
A Prospective, Multicenter, Randomized, Open Label, Active Controlled, Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Dose Combination (FDC) of Doxycycline Hyclate and Metformin Hydrochloride (10%w/w + 1%w/w) Gel in the Treatment Of Adults With Periodontitis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
DRL-IND-NDA01-DXMF/2019; Version 3.0, dated 10/02/2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Piyush Agarwal
Designation
Head - Clinical Development & Clinical Strategy
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal TELANGANA 500090 India
Medchal TELANGANA 500090 India
Phone
Fax
Email
piyushagarwal@drreddys.com
Details of Contact Person Scientific Query
Name
Dr Srinivas Shenoy
Designation
Expert- Clinical Development
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal TELANGANA 500090 India
Medchal TELANGANA 500090 India
Phone
Fax
Email
srinivasshenoyb@drreddys.com
Details of Contact Person Public Query
Name
Vipul Modh
Designation
Specialist-Clinical and Medical Operations
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal TELANGANA 500090 India
Medchal TELANGANA 500090 India
Phone
Fax
Email
vipulmodh@drreddys.com
Source of Monetary or Material Support
Dr. Reddys Laboratories Limited, Integrated Product Development, Innovation Plaza, Survey No
42, 45 & 46, Bachupally Village, Bachupally Mandal, Medchal Malkajgiri District, Hyderabad 500
090, Telangana, India
Primary Sponsor
Name
Dr Reddys Laboratories Limited
Address
IPDO, Innovation plaza, Bachupally village, Bachupally Mandal,
Hyderabad, Medchal Malkajgiri District, 500090, Telangana, India
SPS Room, 2nd Floor, Department of Periodontology, AMC-MET Dental College and Hospital, Bhalakiya Mill Compound, Opp. Anupam Cinema, Khokhra, Ahmedabad, Gujarat - 380006
Ahmadabad GUJARAT
9979667676
beladave@gmail.com
Dr Sashi Kiran R
BGS Gleanagles Global Hospitals, Bengaluru
1st Floor, OPD, Dental Department, BGS Gleanagles Global Hospitals,
#67, Uttarahilli main road kengeri, Bengaluru, karnataka, India - 560060 Bangalore KARNATAKA
9742405614
drshashi.kr25@gmail.com
Dr Mayank Hans
ESIC Medical College and Hospital, Faridabad
Room No. 1039, 1st Floor. Department of Dentistry, OPD Building, ESIC Medical College and Hospital, NH3, NIT, Faridabad, Haryana, India. 121001
Faridabad HARYANA
9818588411
mayankhans@rediffmail.com
Dr Shachi Snehalbhai Shah
Health and Care Foundation Hospital, Ahmedabad
Room No. 22, 2nd Floor, Dental Department, Health and Care Foundation Hospital, Indukaka Ipcowala Sewa Sansthan, Pavansut Society, Opp. Rajwadu, B/H Sunflower School, Jivraj Park, Ahmedabad, Gujarat - 380051 Ahmadabad GUJARAT
9974309049
shachishah5494@gmail.com
Dr Monali Shah
K. M. Shah Dental College and Hospital, Waghodia
Department of periodontology, K. M. Shah Dental College and Hospital, Sumandeep Vidyapeeth Deemed to be University, At & Po Piparia, Ta. Waghodia, Dist. Vadodara, 391760, Gujarat, India
Vadodara GUJARAT
9824003228
smonali2011@gmail.com
Dr Umesh Pratap Verma
King Georges Medical Univesity, Lucknow
5th Floor, Department of Periodontology, King Georges Medical Univesity, Shahmeena Road, Chowk, Lucknow - 226003, Uttar Pradesh, India Lucknow UTTAR PRADESH
9450195422
Umeshverma4@yahoo.com
Dr Sangeeta Umesh Nayak
Manipal College of Dental Sciences, Mangaluru
Room No. 4, Department of Periodontolgy, Manipal College of Dental Science, Light House Hill Road, Mangaluru - 575001, Karnataka, India
Dakshina Kannada KARNATAKA
9880718371
sangeeta.nayak@manipal.edu
Dr Pratibha Gopalkrishna
Manipal College of Dental Sciences, Manipal
Room No. 3, Department of Periodontology, Manipal College of Dental Sciences,
Affiliated to Manipal Academy of Higher Education, Manipal, Karnataka - 576104, India Udupi KARNATAKA
9448724121
pratibha.pk@manipal.edu
Dr Shruti Tandon
Maulana Azad Institute of Dental Sciences, New Delhi
Room No. 613 6th Floor, Department of Periodontology, Maulana Azad Institute of Dental Sciences, Bahadur Shah, Zafar Marg, New Delhi-122002
New Delhi DELHI
9654700982
tandonshruti16@gmail.com
Dr Soma Halder
Medical College and Hospital, Kolkata
Department of Dentistry, Medical College and Hospital 88, College street Kolkata - 700073, West Bengal, India
Kolkata WEST BENGAL
9475679714
somahalderortho2@gmail.com
Dr Arbind Kumar Sharma
Post Graduate lnstitute of Dental Education And Research, IGIMS, Patna
Chief Chamber, Ground Floor, Indira Gandhi Institute of Medical Sciences,
Sheikhpura, Patna, Bihar-8000 14
Patna BIHAR
8544401070
arbindsharmaprof@gmail.com
Dr Tirthankar Debnath
R. Ahmed Dental College & Hospital, Kolkata
R. Ahmed Dental College & Hospital,114, Acharya Jagdish Chandra Bose Rd, Kolkata, West Bengal 700014
Kolkata WEST BENGAL
9123723443
drtdebnath2010@gmail.com
Dr Priyanka Jaiswal
Sharad Pawar Dental College and Hospital, Sawangi (Meghe), Wardha
Room No. 003, Ground Floor, Department of Periodintics, Sharad Pawar Dental College, Sawangi (Meghe), Wardha-442004, Maharashtra, India
Nagpur MAHARASHTRA
9960713010
priyanka.banode@gmail.com
Dr C V Divyambika
Sri Ramachandra Hospital, Chennai
Basement Dental College , Sri Ramachandra Hospital, No. 1 Ramachandra Nagar, Porur, Chennai - 600116, Tamil Nadu, India Chennai TAMIL NADU
9840323553
cvdivyambika@sriramachandra.edu.in
Dr Rajiv Nidasale Puttaswamaiah
Vokkaligara Sangha Dental college and Hospital, Bangalore
Room No. 5 Department of Periodointics, Vokkaligara Sangha Dental college and Hospital, K.R Road, VV puram, Bangalore, Karnataka - 650004, India
Bangalore KARNATAKA
MAHE Ethics Committee, Manipal Academy of Higher Education, Manipal
Approved
MAHE Ethics Committee, Manipal Academy of Higher Education, Manipal
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K054||Periodontosis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Fixed Dose Combination (FDC) of Doxycycline Hyclate and Metformin Hydrochloride Gel (Prototype 2)
Single Dose of Prototype 2 Fixed Dose Combination (FDC) of Doxycycline Hyclate and Metformin Hydrochloride (10%W/W + 1% W/W) gel to be administered on randomization visit (Day 0)
Intervention
Single Dose Fixed Dose Combination (FDC) of Doxycycline Hyclate and Metformin Hydrochloride gel (Prototype 1)
Single Dose Prototype 2 Fixed Dose Combination (FDC) of Doxycycline Hyclate and Metformin Hydrochloride (10%W/W + 1% W/W) gel to be administered on randomization visit (Day 0)
Comparator Agent
Standard of care- Scaling and root planing
Standard of care- Scaling and root planing (SRP) procedure as per Institutional practice to be performed on randomization visit(Day 0)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female subjects between 18 – 65 years of age (Both inclusive), with a clinical diagnosis of Stage III or stage IV periodontitis characterized by ≥5 mm interdental clinical attachment loss (CAL) and pockets measured with probing depth (PD) ≥6 mm.
2. Subjects with ≥14 natural teeth.
3. Willing to provide written informed consent and comply with study instructions for its duration.
4. In good general health other than periodontitis according to medical history, physical examination and clinical judgment undertaken by investigator.
5. Non-alcoholics & Non-smokers / Ex-smokers (at least 2years of abstinence)
6. Able to follow written and verbal instructions, perform oral hygiene as specified in the protocol, & return to the center for specified study visits.
7. Negative serum pregnancy test prior to beginning therapy and agreement to use adequate birth control during the study for females of child-bearing potential.
ExclusionCriteria
Details
1. Known hypersensitivity to Doxycycline Hyclate or other Tetracyclines and/or Metformin/Biguanide group or any excipients or any related drug or any substance.
2. Compromised renal function (as indicated by serum creatinine levels > 1.5 times ULN)
3. Ongoing systemic cancer chemotherapy and/or radiation therapy.
4. Known history or presence of tobacco chewing and / or betel nut usage.
5. Known history or presence of clinically significant acute or chronic illness such as Diabetes Mellitus, Neutropenia (Severe and/or acquired), Inflammatory Bowel Disease (IBD), Osteoporosis, Hyperparathyroidism, Oral candidiasis, Rheumatic fever, Cancer, Connective tissue disease (such as Systemic Lupus Erythematosus (SLE), Lichen Planus, Rheumatoid Arthritis (RA), Systemic sclerosis (scleroderma) and Ankylosing Spondylitis) etc.,
6. Presence of clinically significant cardiovascular, Hepatic, Pulmonary, Neurologic, Renal or Psychiatric disorder, or clinically significant laboratory abnormalities as judged by investigator
7. A positive hepatitis screen including positive test result for hepatitis B surface antigen and/or HCV antibodies & HIV antibody (I & II).
8. Prior/Ongoing treatment with the following medications:
Mouthwash with known antibacterial properties (regularly within 1 month prior to baseline examination)
ï€ Antimicrobials (6 weeks prior to baseline examination)
ï€ Sulfasalazine and/or drugs causing gingival hyperplasia such as Phenytoin and other anticonvulsants (Phenobarbital, Lamotrigine, Vigabatrin, Ethosuximide, Topiramate and Primidone) or Cyclosporine or Calcium Channel Blockers (CCB) such as Nifedipine, Amlodipine, and Verapamil) (within 3 months prior to baseline examination)
ï€ Systemic, topical application inside oral cavity & inhalational corticosteroids or Oral Bisphosphonates (6 months prior to baseline examination)
ï€ Patients on systemic metformin therapy
9. Any need for systemic or local antibiotic prophylaxis prior to enrollment (e.g., for recent orthopedic implants, Patients with a prosthetic heart valve etc.,)
10. Ongoing pregnancy, lactation or plan of pregnancy during the proposed study period or not using an acceptable method of birth control (IUD, Norplant, Depo-Provera, Diaphragm, or Condom).
11. Enrolled in any other investigational medication study currently, or within the last 6 months.
12. Investigators opinion that subject is not suitable for the study otherwise.
13. Periodontitis disease specific exclusion criteria:
a. Accumulation of substantial sub-gingival calculus defined as 80% or greater surfaces of the dentition having dental calculus. (Process of assessing this will be explained in separate study specific dental assessment manual)
b. Undergone
ï€ SRP (Scaling and Root Planning) therapy (less than 6 months prior to base line examination)
ï€ Surgical periodontal treatment (within past 6 months or scheduled during the study) or
ï€ Orthodontic therapy including removable partial denture (ongoing or scheduled during the study)
c. Requirement of restorative and endodontic therapy during the study period
d. Periodontal sites with Class III furcation
e. CAL is only due to local factor
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Mean Change in clinical attachment loss (CAL)
Day 0 and Day 90
Secondary Outcome
Outcome
TimePoints
Mean Change in clinical attachment loss (CAL)
Day 0, Day 28, Day 60
Mean Change in probing depth (PD)
Day 0, Day 28, Day 60, Day 90
Change in Modified Papillary Bleeding Index (MPBI) from Baseline
Day 0, Day 28, Day 60, Day 90
Change in New Method of Plaque Scoring (NMPS) from Baseline
Day 0, Day 28, Day 60, Day 90
Assessment of self-completed Oral Health Impact Profile (OHIP) ‑14 questionnaire from Baseline
Day 0 and Day 90
Exploratory Endpoint : Percentage change in Intra Bony Defect (IBD) / Radiographic Bone Loss (RBL)
Day 0 and Day 90
Exploratory Endpoint :To evaluate release profile of Doxycycline (In GCF & In saliva) and Metformin (In GCF) with each prototype (T1 & T2) in 12 subjects in each arm to assess.
GCF and Saliva Collection will be done at pre-dose
to 168/192 hours
Target Sample Size
Total Sample Size="186" Sample Size from India="186" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
27/03/2023
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="9" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
Nil
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is planned to evaluate the efficacy, and safety of fixed dose combination (FDC) of doxycycline hyclate and metformin hydrochloride (10%w/w + 1%w/w) gel in the treatment of adults with periodontitis. Male and non-pregnant female subjects (18-65 years of age) with clinical diagnosis of Stage III or stage IV periodontitis will be included in tral