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A Clinical Study to Evaluate the Safety, Tolerability, PK, PD, and Efficacy of KBP-089 in Patients With T2DM

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ClinicalTrials.gov Identifier: NCT03907202
Recruitment Status : Recruiting
First Posted : April 8, 2019
Last Update Posted : April 8, 2019
Sponsor:
Collaborators:
Eli Lilly and Company
Nordic Bioscience A/S
Profil Institut für Stoffwechselforschung GmbH
Information provided by (Responsible Party):
KeyBioscience AG

Brief Summary:

KeyBioscience is developing KBP-089, a dual activator of both the amylin and calcitonin receptors, for the treatment of type II diabetes mellitus, using a subcutaneous injectable mode of administration.

This is a double-blind, placebo-controlled, randomised, multiple-ascending dose phase I trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of KBP-089 in patients with type 2 diabetes, who are on stable therapy with metformin.

Subjects will receive daily subcutaneous injections in the abdomen over a period of 28 days. The planned maximum doses of KBP-089 to be investigated in the trial are 20 µg in cohort 1, 60 µg in cohort 2, and 150 µg in cohort 3. For cohort 1, the dose is planned to be escalated every 7 ±1 days, and for cohort 2 and cohort 3, every 3 days. Doses may be modified according to individual tolerability, but the dose regimen will not exceed 28 days.

The IMP is administered by daily subcutaneous injections taken in the morning before breakfast.

The trial is performed in Germany and at least 36 patients will be enrolled in the trial. The trial will be randomised 1:1:1 between maximum doses of KBP-089 of 20 µg, 60 µg, 150 µg and placebo. Within each of the three cohorts, 12 patients will be randomised 3:1 to KBP-089 and placebo.


Condition or disease Intervention/treatment Phase
Type II Diabetes Mellitus Drug: Daily injection of KBP/placebo for up to 28 days Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised, patient-blind, investigator-blind, placebo-controlled, multiple ascending dose study. There will be 3 cohorts in which patients are randomised to receive either treatment with KBP-089 or placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

To preserve the blinding of the study for KBP-089 and placebo, all study site personnel, except pharmacy staff who prepare and dispense study medication, and the Sponsor's medical monitor who interacts with site personnel will be blinded to treatment allocation. Blinding of KBP-089 and placebo will be maintained throughout the conduct of the trial until after the completion of the trial and final data review.

Treatment assignment will be kept strictly confidential and accessible only to authorised persons until after the time of unblinding. Codes with treatment assignment will, however, be readily available to the blinded personnel in case of an emergency.

Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled, Randomised, Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KBP-089 in Patients With Type II Diabetes
Actual Study Start Date : April 17, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: KBP-089

Three cohorts:

  • Cohort 1: starting dose 5 µg, maximum dose 20 µg, uptitration step 7 days, dose increment 5 µg
  • Cohort 2: starting dose 7.5 µg, maximum dose 60 µg, uptitration step 3 days, dose increment 7.5 µg
  • Cohort 3: starting dose 5 µg, maximum dose 120 µg, uptitration step 3 days, dose increment 5, 10, 15 and 20 µg
Drug: Daily injection of KBP/placebo for up to 28 days
Daily sub-cutaneous injection of KBP-089/Placebo into a lifted skin fold of the abdominal wall.The injection will be administered in the morning before breakfast.

Placebo Comparator: Placebo
For all the cohorts, sentinel dosing for the first two patients will be performed 1:1 in a blinded manner.
Drug: Daily injection of KBP/placebo for up to 28 days
Daily sub-cutaneous injection of KBP-089/Placebo into a lifted skin fold of the abdominal wall.The injection will be administered in the morning before breakfast.




Primary Outcome Measures :
  1. Treatment Emergent Adverse Events (TEAEs). [ Time Frame: Day -1 to day 28 ]
    All TEAEs will be coded using MedDRA and summarized by treatment and dose.

  2. Vital sign - Blood Pressure. [ Time Frame: Day -1 to day 28 ]

    Diastolic and systolic blood pressure (mmHg) are measured after at least 5 min rest in a supine position.

    Vital signs will be summarised by descriptive statistics by treatment, dose and timepoint.


  3. Vital sign - Pulse (beats per min). [ Time Frame: Day -1 to day 28 ]
    measured after at least 5 min rest in a supine position. Vital signs will be summarised by descriptive statistics by treatment, dose and timepoint.

  4. Vital sign - Body Temperature. [ Time Frame: Day -1 to day 28 ]
    Body temperature, tympanic (in Celcius). Vital signs will be summarised by descriptive statistics by treatment, dose and timepoint.

  5. Vital sign - Respiratory frequency. [ Time Frame: Day -1 to day 28 ]
    Respiratory frequency measured as breaths per min. Vital signs will be summarised by descriptive statistics by treatment, dose and timepoint.

  6. Electrocardiogram (ECG) - PQ interval. [ Time Frame: Day -1 to day 28 ]
    PQ interval (in msec) and any abnormality will be recorded and described in the CRF including the Investigator's assessment of clinical significance ('abnormal, not clinically significant' or 'abnormal, clinically significant').

  7. Electrocardiogram (ECG) - QRS complex. [ Time Frame: Day -1 to day 28 ]
    QRS interval (in msec) and any abnormality will be recorded and described in the CRF including the Investigator's assessment of clinical significance ('abnormal, not clinically significant' or 'abnormal, clinically significant').

  8. Electrocardiogram (ECG) - QT interval. [ Time Frame: Day -1 to day 28 ]
    QT interval (in msec) and any abnormality will be recorded and described in the CRF including the Investigator's assessment of clinical significance ('abnormal, not clinically significant' or 'abnormal, clinically significant').

  9. Safety laboratory parameter - lipids. [ Time Frame: Day -1 to day 28 ]

    Standard Lipid assessments will be summarized by treatment (including dose) using descriptive statistics (number, mean, standard deviation, minimum, median and maximum).

    (Lipid parameters measured: Total cholesterol, High-density lipoprotein (HDL) cholesterol, Low-density lipoprotein (LDL) cholesterol, Triglycerides).


  10. Safety laboratory parameter - haematology. [ Time Frame: Day -1 to day 28 ]

    Standard Biochemistry assessments will be summarized by treatment (including dose) using descriptive statistics (number, mean, standard deviation, minimum, median and maximum).

    (Haematology parameters measured: Haematocrit, Haemoglobin, Erythrocytes, Mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH), Mean corpuscular haemoglobin concentration (MCHC), Thrombocytes (platelets), Leucocytes, Neutrophile granulocytes (total count and relative), Lymphocytes (total count and relative), Monocytes (total count and relative), Eosinophile granulocytes (total count and relative), Basophile granulocytes (total count and relative))


  11. Safety laboratory parameter - coagulation. [ Time Frame: Day -1 to day 28 ]

    Standard coagulation assessments will be summarized by treatment (including dose) using descriptive statistics (number, mean, standard deviation, minimum, median and maximum).

    (coagulation parameters measured: International normalised ratio (INR), Activated partial thromboplastin time (APTT)


  12. Safety laboratory parameter - urinalysis. [ Time Frame: Day -1 to day 28 ]

    Standard Biochemistry assessments will be summarized by treatment (including dose) using descriptive statistics (number, mean, standard deviation, minimum, median and maximum).

    (Urinalysis parameters measured: Protein, Glucose, Erythrocytes, Leucocytes, pH, Ketones)



Secondary Outcome Measures :
  1. Pharmacokinetic Evaluation - KBP-089 Area Under Curve. [ Time Frame: Day -1 to day 28 ]
    PK parameter (AUC 0-24) will be derived by non-compartmental analysis of the plasma concentration data for KBP-089

  2. Pharmacokinetic Evaluation - KBP-089 Cmax. [ Time Frame: Day -1 to day 28 ]
    PK parameter (Cmax) will be derived by non-compartmental analysis of the plasma concentration data for KBP-089

  3. Gastric emptying - Paracetamol Cmax. [ Time Frame: Day -1 to day 28 ]
    Gastric emptying is measured using paracetamol Cmax at baseline (Day -1), Day 1, and Day 28 for Cohorts 1 and 2 only

  4. Gastric emptying - Paracetamol Tmax. [ Time Frame: Day -1 to day 28 ]
    Gastric emptying is measured using paracetamol Tmax at baseline (Day -1), Day 1, and Day 28 for Cohorts 1 and 2 only

  5. Gastric emptying - Paracetamol Area Under Curve (AUC). [ Time Frame: Day -1 to day 28 ]
    Gastric emptying is measured using paracetamol AUC at baseline (Day -1), Day 1, and Day 28 for Cohorts 1 and 2 only

  6. Fasting and postprandial glucose concentration. [ Time Frame: Day -1 to day 28 ]
    Fasting and postprandial glucose following OGTT at baseline (Days -1) and Day 28

  7. Fasting and postprandial insulin concentration. [ Time Frame: Day -1 to day 28 ]
    Insulin following OGTT at baseline (Days -1) and Day 28

  8. Fasting and postprandial C-peptide concentration. [ Time Frame: Day -1 to day 28 ]
    Fasting and postprandial C-peptide following OGTT at baseline (Days -1) and Day 28

  9. Fasting and postprandial glucagon concentration. [ Time Frame: Day -1 to day 28 ]
    Fasting and postprandial glucagon following OGTT at baseline (Days -1) and Day 28

  10. Body weight. [ Time Frame: Day -1 to day 28 ]
    Body weight at Day -1 (baseline) and Day 28 (in kg)

  11. N-(1-deoxy)-fructosyl-haemoglobin (HbA1c). [ Time Frame: Day -1 to day 28 ]
    HbA1c at Day -1 (baseline) and Day 28 (in mmol/mol)

  12. Fridericia's corrected QT interval (QTcF). [ Time Frame: Day 1 to day 27 ]
    Fridericia's corrected QT interval (QTcF) at Day 1 and Day 27 (in msec)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedures that would not have been performed during normal management of the patient).
  • Male or female patient with T2DM.
  • Age between 18 and 64 years, both inclusive.
  • Body Mass Index (BMI) >= 25.0 kg/m^2.
  • HbA1c >= 7 and <=9.5%.
  • Stable therapy with metformin ± treatment with a second oral anti-diabetes drug (OAD) belonging to the class of dipeptidyl-peptidase 4 (DPP-4) inhibitors or sulfonylureas for at least 2 months prior to inclusion into the trial or not treated with glucose-lowering medications. Patients who are receiving stable treatment with a second OAD will be asked to discontinue the DPP-4 inhibitor or a sulfonylurea for at least 14 days prior the Initial Inpatient Dosing Visit.
  • Considered generally healthy (apart from T2DM) upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator.

Exclusion Criteria:

  • Known or suspected hypersensitivity or allergy to paracetamol or related products.
  • Prior treatment with a dual amylin and calcitonin receptor agonist (DACRA) or salmon calcitonin.
  • Receipt of any medicinal product in clinical development within 30 days or 5 half-lives of the medicinal product (whichever is longer) before randomisation in this trial.
  • History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
  • Any history or presence of clinically relevant cardiovascular, pulmonary, respiratory, gastrointestinal, hepatic, renal, metabolic, endocrinological (with the exception of conditions associated with diabetes mellitus), haematological, dermatological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness as judged by the Investigator.
  • Medically unable or unwilling to discontinue current anti-diabetic therapy with DPP-4 inhibitor or sulfonylurea for at least 14 days prior to admission to the research facility (Day -2) and remain off medication until the follow-up visit. Patients taking metformin therapy at entry will continue their metformin at the usual individual dose throughout the trial.
  • Have had a significant change in weight, defined as a gain or loss of at least 5% body weight in the 3 months prior to screening.
  • A positive result in the alcohol and/or urine drug screen at the screening visit.
  • Positive to the screening test for Hepatitis Bs antigen (HBsAg) or Hepatitis C antibodies and/or a positive result to the test for human immunodeficiency virus (HIV)-1/2 antibodies or HIV-1 antigen.
  • Have had a blood transfusion or severe blood loss within the past 6 months or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or have a hemoglobin value <11 g/dL (males) or <10 g/dL (females), or any other condition known to interfere with HbA1c methodology.
  • Blood donation or blood loss of more than 500 mL within the last 3 months or any blood donation within the last month prior to screening.
  • Females of childbearing potential.
  • Males with pregnant partners.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03907202


Contacts
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Contact: Regulatory Nordic Bioscience, MSc +45 4452 5252 regulatory@nordicbioscience.com

Locations
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Germany
Profil Institut für Stoffwechselforschung GmbH Recruiting
Neuss, Germany, D-41460
Contact: Tim Heise, MD.         
Sponsors and Collaborators
KeyBioscience AG
Eli Lilly and Company
Nordic Bioscience A/S
Profil Institut für Stoffwechselforschung GmbH
Investigators
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Principal Investigator: Tim Heise, MD Profil Institut für Stoffwechselforschung GmbH

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Responsible Party: KeyBioscience AG
ClinicalTrials.gov Identifier: NCT03907202     History of Changes
Other Study ID Numbers: KBP089/CD/002
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by KeyBioscience AG:
Sub-cutaneous injection
Metformin
KBP-089
randomised
placebo-controlled
multiple-ascending dose

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases