Type 2 Diabetes MellitusPhase 1NCT03392961
Effect of Dosing Time and Meal on IN-105 (Insulin Tregopil) PK and PD
A Phase 1 study testing IN-105 (Insulin Tregopil) in people with Type 2 Diabetes Mellitus, run by Biocon Limited.
Trial summary
A study to evaluate the PK and PD of oral IN-105 (Insulin Tregopil) w.r.t. time of dosing prior to meal, duration between meals and type of meal . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- IN-105 (Insulin Tregopil)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- 27 Mar 2014to 1 Jul 2014
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient should have an established diagnosis of T2DM per ADA 2013 criteria for at least 1 year prior to screening and are on metformin treatment for at least a month before screening.
- Body mass index (BMI) of 18.5 to 40.00 kg/m2, both inclusive
- Glycosylated hemoglobin (HbA1c) ≤ 9.5%.
- Hemoglobin ≥9.0 g/dL.
- No clinically significant abnormality in the ECG at screening.
- Fasting plasma glucose levels less than 140 mg/dL at screening.
- The patient should be ready to give a written and signed informed consent before starting any protocol-specific procedures.
Who cannot join
- History of hypersensitivity to insulins or insulin analogues.
- Evidence of the following (either due to improper diabetes control or due to secondary complications following diabetes).
- History of ≥2 episodes of severe hypoglycemia within 6 months before screening or history of hypoglycemia unawareness as judged by the investigator.
- History of ≥1 episodes of hyperglycemic hyperosmolar state or emergency room visits for uncontrolled diabetes leading to hospitalization in the 6 months prior to screening.
- History of limb amputation as a complication of diabetes during his/her lifetime or any vascular procedure during the 1 year prior to screening.
- History of diabetic foot or diabetic ulcers in the past 1 year prior to screening.
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- History of severe form of neuropathy or cardiac autonomic neuropathy (determined when obtaining patient history).
- Presence of any of the following:
- Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HBsAg) or hepatitis C infection at screening.
- Any clinically significant abnormality in the safety laboratory tests conducted at screening.
- Impaired hepatic function at screening [alanine transaminase (ALT) or aspartate aminotransferase (AST) value >2 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range] which investigator considers clinically significant.
- Evidence of clinically significant chronic renal disease (e.g. nephrotic syndrome, diabetic nephropathy) as assessed by the investigator at screening
- History or use of the following:
- Patients on OADs other than metformin for previous three months prior to screening.
- Patients who have received ≥14 consecutive days of oral, intravenous, or inhaled glucocorticoid therapy within the past 1 year or have received steroids by any route within 4 weeks immediately preceding screening visit (intra-nasal, intra ocular, and topical steroid use is allowed).
- Receipt of another investigational drug in the 4 weeks prior to screening, or within 5 half-lives of the another investigational drug at screening visit (whichever is longer), or scheduled for another investigational drug during the current study period.
About this study
Official title: To Assess the Pharmacokinetics and Pharmacodynamics of IN-105 in Relation to the Pre-meal Dosing Time, Between-meal Interval and Type of Meal - A Phase 1, Three Cohort, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients
A study to evaluate the PK and PD of oral IN-105 (Insulin Tregopil) w.r.t. time of dosing prior to meal, duration between meals and type of meal .
Read the detailed description
A Phase 1, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients to evaluate the effect of pre-meal dosing time, inter-meal interval and meal composition on the PK and PD of IN-105 (Insulin Tregopil), an oral insulin; conducted in 3 sequential cohorts in an adaptive manner .
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- IN-105 (Insulin Tregopil), Placebo comparator
- Keywords
- Oral insulin, Dosing time, Insulin concentration, Prandial insulin, Post Prandial Glucose (PPG)
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IN-105 (Insulin Tregopil)Drug
15 mg strength tablets for oral use used at a dose of 30 mg
Placebo comparatorOther
Placebo tablet for oral use
| Study group | Role | What they receive |
|---|---|---|
| IN-105 (Insulin Tregopil) | Experimental | Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal.
Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively.
Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F). Receives: Drug: IN-105 (Insulin Tregopil) |
| Placebo tablet | Placebo comparator | Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal.
Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively.
Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F). Receives: Other: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1)
Area under the plasma concentration-time curve (AUC0-last; from dosing time to 180 minutes post meal, extrapolated) after single dose administration in the 30 ,20 and 10 minute pre-meal dosing groups
Measured: from dosing time to 180 minutes post meal, extrapolated
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 1)
The maximum observed plasma drug concentration after single dose administration (Cmax)
Measured: from dosing time to 180 minutes post meal
Glucose AUC0-t will be assessed (Cohort 1)
Glucose AUC0-t [AUC both above and below the baseline values]
Measured: from dosing time to 180 minutes post meal
Glucose concentration (Cmin) will be assessed (Cohort 1)
Minimum observed glucose concentration (Cmin)
Measured: from dosing time to 180 minutes post meal
Glucose concentration (Tmin) will be assessed (Cohort 1)
Time of minimum observed glucose concentration (Tmin)
Measured: from dosing time to 180 minutes post meal
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 2)
Area under the plasma concentration-time curve (AUC0-last; time of dosing to 180 minutes post dose, extrapolated) after single dose administration in morning and afternoon in the 4, 5 and 6 h inter-meal interval groups.
Measured: time of dosing to 180 minutes post dose,extrapolated
The maximum observed plasma drug concentration (Cmax) will be assessed. (Cohort 2)
The maximum observed plasma drug concentration after single dose administration (Cmax)
Measured: time of dosing to 180 minutes post dose
Glucose AUC0-t will be assessed (Cohort 2)
Glucose AUC0-t [AUC both above and below the baseline values]
Measured: time of dosing to 180 minutes post dose
Glucose concentration (Cmin) will be assessed (Cohort 2)
Minimum observed glucose concentration (Cmin)
Measured: time of dosing to 180 minutes post dose
Glucose concentration (Tmin) will be assessed (Cohort 2)
Time of minimum observed glucose concentration (Tmin)
Measured: time of dosing to 180 minutes post dose
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 3)
Area under the plasma concentration-time curve (AUC0-last) for high-fat, high-fibre and ADA meal groups after single dose administration in morning and afternoon
Measured: time of dosing to 180 minutes post dose,extrapolated
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 3)
The maximum observed plasma drug concentration after single dose administration (Cmax)
Measured: time of dosing to 180 minutes post dose
Glucose AUC0-t will be assessed (Cohort 3)
Glucose AUC0-t [AUC both above and below the baseline values]
Measured: time of dosing to 180 minutes post dose
Glucose concentration (Cmin) will be assessed. (Cohort 3)
Minimum observed glucose concentration (Cmin)
Measured: time of dosing to 180 minutes post dose
Glucose concentration (Tmin) will be assessed. (Cohort 3)
Time of minimum observed glucose concentration (Tmin)
Measured: time of dosing to 180 minutes post dose
Secondary outcomes (1)
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
An adverse event is any untoward medical event including hypoglycemia that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measured: Through study completion, approximately 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start27 Mar 2014
- Primary completion1 Jul 2014
- Study completion1 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies 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
- Crossover
- Model description
- 3 Cohorts Cohort 1: 5 periods, 4 treatments and 5 sequences with a partial replicate crossover design Cohort 2: 6 periods, 6 treatments and 6 sequences in a cross-over design Cohort 3: 6 periods, 6 treatments and 6 sequences in a cross over design
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biocon Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Juan Carlos Rondon, M.D,JD, Principal investigator, Elite Research Institute, 15705 NW 13th Avenue, Miami, Florida 33169
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03392961
- Sponsor's protocol ID
- IN-105-DM-01-G-14
- Status last verified
- Jan 2018
- First submitted
- 19 Dec 2017
- Last updated
- 23 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Khedkar A, Lebovitz H, Fleming A, Cherrington A, Jose V, Athalye SN, Vishweswaramurthy A. Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus. Clin Pharmacol Drug Dev. 2020 Jan;9(1):74-86. doi: 10.1002/cpdd.730. Epub 2019 Aug 7.
PubMed 31392840
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Assess the Pharmacokinetics and Pharmacodynamics of IN-105 in Relation to the Pre-meal Dosing Time, Between-meal Interval and Type of Meal - A Phase 1, Three Cohort, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients
- ClinicalTrials.gov ID
- NCT03392961
- Acronym / sponsor ID
- IN-105-DM-01-G-14
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Oral insulin, Dosing time, Insulin concentration, Prandial insulin, Post Prandial Glucose (PPG)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Biocon LimitedIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2014 (actual)
- Primary completion
- 1 Jul 2014 (actual)
- Study completion
- 1 Jul 2014 (actual)
- First posted
- 8 Jan 2018 (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.
A study to evaluate the PK and PD of oral IN-105 (Insulin Tregopil) w.r.t. time of dosing prior to meal, duration between meals and type of meal .
Detailed description
A Phase 1, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients to evaluate the effect of pre-meal dosing time, inter-meal interval and meal composition on the PK and PD of IN-105 (Insulin Tregopil), an oral insulin; conducted in 3 sequential cohorts in an adaptive manner .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 3 Cohorts Cohort 1: 5 periods, 4 treatments and 5 sequences with a partial replicate crossover design Cohort 2: 6 periods, 6 treatments and 6 sequences in a cross-over design Cohort 3: 6 periods, 6 treatments and 6 sequences in a cross over design
| Arm | Type | Receives |
|---|---|---|
| IN-105 (Insulin Tregopil) | Experimental | Drug: IN-105 (Insulin Tregopil)Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal. Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively. Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F). |
| Placebo tablet | Placebo comparator | Other: Placebo comparatorCohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal. Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively. Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient should have an established diagnosis of T2DM per ADA 2013 criteria for at least 1 year prior to screening and are on metformin treatment for at least a month before screening.
- Body mass index (BMI) of 18.5 to 40.00 kg/m2, both inclusive
- Glycosylated hemoglobin (HbA1c) ≤ 9.5%.
- Hemoglobin ≥9.0 g/dL.
- No clinically significant abnormality in the ECG at screening.
Key exclusion criteria (16 listed)
- History of hypersensitivity to insulins or insulin analogues.
- Evidence of the following (either due to improper diabetes control or due to secondary complications following diabetes).
- Presence of any of the following:
- History or use of the following:
- Receipt of another investigational drug in the 4 weeks prior to screening, or within 5 half-lives of the another investigational drug at screening visit (whichever is longer), or scheduled for another investigational drug during the current study period.
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 |
|---|---|---|
| IN-105 (Insulin Tregopil)15 mg strength tablets for oral use used at a dose of 30 mg | Drug | IN-105 (Insulin Tregopil) |
| Placebo comparatorPlacebo tablet for oral use | Other | Placebo tablet |
Primary outcome
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1)
Time frame: from dosing time to 180 minutes post meal, extrapolated
Area under the plasma concentration-time curve (AUC0-last; from dosing time to 180 minutes post meal, extrapolated) after single dose administration in the 30 ,20 and 10 minute pre-meal dosing groups
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 1)
Time frame: from dosing time to 180 minutes post meal
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose AUC0-t will be assessed (Cohort 1)
Time frame: from dosing time to 180 minutes post meal
Glucose AUC0-t [AUC both above and below the baseline values]
Glucose concentration (Cmin) will be assessed (Cohort 1)
Time frame: from dosing time to 180 minutes post meal
Minimum observed glucose concentration (Cmin)
Glucose concentration (Tmin) will be assessed (Cohort 1)
Time frame: from dosing time to 180 minutes post meal
Time of minimum observed glucose concentration (Tmin)
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 2)
Time frame: time of dosing to 180 minutes post dose,extrapolated
Area under the plasma concentration-time curve (AUC0-last; time of dosing to 180 minutes post dose, extrapolated) after single dose administration in morning and afternoon in the 4, 5 and 6 h inter-meal interval groups.
The maximum observed plasma drug concentration (Cmax) will be assessed. (Cohort 2)
Time frame: time of dosing to 180 minutes post dose
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose AUC0-t will be assessed (Cohort 2)
Time frame: time of dosing to 180 minutes post dose
Glucose AUC0-t [AUC both above and below the baseline values]
Glucose concentration (Cmin) will be assessed (Cohort 2)
Time frame: time of dosing to 180 minutes post dose
Minimum observed glucose concentration (Cmin)
Glucose concentration (Tmin) will be assessed (Cohort 2)
Time frame: time of dosing to 180 minutes post dose
Time of minimum observed glucose concentration (Tmin)
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 3)
Time frame: time of dosing to 180 minutes post dose,extrapolated
Area under the plasma concentration-time curve (AUC0-last) for high-fat, high-fibre and ADA meal groups after single dose administration in morning and afternoon
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 3)
Time frame: time of dosing to 180 minutes post dose
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose AUC0-t will be assessed (Cohort 3)
Time frame: time of dosing to 180 minutes post dose
Glucose AUC0-t [AUC both above and below the baseline values]
Glucose concentration (Cmin) will be assessed. (Cohort 3)
Time frame: time of dosing to 180 minutes post dose
Minimum observed glucose concentration (Cmin)
Glucose concentration (Tmin) will be assessed. (Cohort 3)
Time frame: time of dosing to 180 minutes post dose
Time of minimum observed glucose concentration (Tmin)
1 secondary outcome
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: Through study completion, approximately 3 months.
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 23 Jan 2018.
- Derived from this study: PubMed 31392840Khedkar A, Lebovitz H, Fleming A, Cherrington A, Jose V, Athalye SN, Vishweswaramurthy A. Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus. Clin Pharmacol Drug Dev. 2020 Jan;9(1):74-86. doi: 10.1002/cpdd.730. Epub 2019 Aug 7.
- Individual participant dataSharing planned: Undecided
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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.
Juan Carlos Rondon, M.D,JD principal investigator
Elite Research Institute, 15705 NW 13th Avenue, Miami, Florida 33169
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IN-105 (Insulin Tregopil) in people with Type 2 Diabetes Mellitus, run by Biocon Limited.
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 7 inclusion and 16 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 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1) (time frame: from dosing time to 180 minutes post meal, extrapolated). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03392961, which also lists 1 linked publication.
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 23 Jan 2018.