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Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PKs) of ZYDPLA1 Following Oral Administration in Healthy Volunteers

1 december 2015 bijgewerkt door: Zydus Lifesciences Limited

A Randomized, Double-blind, Placebo-controlled Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZYDPLA1, a Novel DPP- IV Inhibitor, Following Oral Administration in Healthy Volunteers

This First in Human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYDPLA1 in normal healthy adult volunteers.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide (GLP-1) are incretin hormones, which stimulate glucose dependent insulin secretion, inhibit glucagon secretion, delay gastric emptying, suppress appetite and improve peripheral glucose uptake and disposal. Dipeptidyl peptidase-IV (DPP-IV) is a serine protease, which selectively cleaves the first two amino acids of GIP and GLP-1 thereby making it inactive. Inhibition of DPP-IV activity elevates endogenous GIP, GLP-1 and insulin levels thereby improving glucose excursion and exhibits antidiabetic activity. Since no orally active GLP-1 agonists are available, clinically orally bioavailable DPP-IV inhibitors hold great potential for the treatment of type 2 diabetes mellitus.

Cadila Healthcare Ltd. developed a novel and orally bioavailable DPP-IV inhibitor (ZYDPLA1). In-vitro studies confirm selective DPPIV inhibitory activity of the ZYDPLA1. Pre-clinical in vivo pharmacodynamic, absorption, distribution, metabolism and excretion (ADME) & toxicological studies showed the promising antidiabetic activity, good exposure and safety profile of ZYDPLA1(in various animal models).

Hence a randomized, double-blind, placebo-controlled first in man trial proposed to evaluate the safety and tolerability of ZYDPLA1 in healthy volunteers.

This study included 4 plans:

i) single dose escalation study ii) multiple dose escalation study, iii) gender effect study and iv) food effect study.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

84

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • California
      • Chula Vista, California, Verenigde Staten, 91911
        • Profil Institute for Clinical Research

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 65 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Healthy male or female between 18 and 65 years of age.
  2. Male subjects must agree to use one of the contraception methods during the study. Male contraceptive options include: Vasectomy, Abstinence requiring the use of contraceptives if becoming sexually active, or double barrier method (condom with spermicide, diaphragm or cervical cap). No Sperm donation for at least up to 90 days after last investigational product.
  3. BMI within the range 18.0 - 30.0 kg/m2 BMI value should be rounded off to one significant digit after decimal point. BMI values should be rounded to the nearest integer (ex. 30.4 rounds down to 30, while 17.5 rounds up to 18).
  4. Capable of giving written informed consent, which includes compliance with protocol.
  5. Corrected QT interval (QTc) interval < 450msec (as measured by QTcF)
  6. For gender effect study, only females with history of sterility or at least 1 year menopause or use of long acting non hormonal contraceptive measures (e.g., intrauterine device) will be recruited. Surgical sterility is defined as either bilateral tubal ligation/occlusion, bilateral oophorectomy or hysterectomy.
  7. Negative Urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, methadone and phencyclidine within 28 days prior to initiation of the study and prior to check-in.

Exclusion Criteria:

  1. Presence or history of pancreatitis at any time {Serum Amylase/Serum Lipase more than significant upper normal limit (≥1.5 times UNL)}
  2. Presence or history of severe gastrointestinal disease in the last 6 months
  3. Presence or history of renal insufficiency at any time {Serum creatinine more than upper normal limit (UNL)}
  4. Active liver disease and/or liver transaminases greater than 1.5 times UNL
  5. History or presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement)
  6. History or presence of any medication in the last 14 days
  7. History or presence of significant alcoholism or drug abuse within the past 1 year
  8. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day)
  9. Difficulty with donating blood or difficulty in accessibility of veins.
  10. Intolerance to venipuncture.
  11. Systolic blood pressure more than 150 mmHg and less than 100 mmHg and diastolic blood pressure more than 90 mmHg
  12. Pulse rate less than 50/minute and more than 100/minute
  13. Any clinically significant laboratory findings during screening
  14. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening as determined by the Principal Investigator.
  15. Major illness and/or major surgery in last 3 months
  16. Volunteers who have participated in any drug research study other than the present trial within the past 30 days (Subjected to Insurance that subject has not participated in long acting drug including new biological entities/new chemical entities/biosimilar products).
  17. Volunteers who have donated one unit (450 mL) of blood in the past 3 months
  18. Positive Alcohol breath analyzer at the time of Screening and Check-in
  19. A positive hepatitis screen (includes subtype B and C) and/or a positive test result for HIV antibody.
  20. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal investigator or Sub-investigator, could contraindicate the study participant's participation in this study.
  21. For gender effect study, female volunteers with following criteria will not be recruited:

    • History of pregnancy or lactation in the past 3 months
    • Fertile female volunteers not protected against pregnancy by adequate long-term anti-fertility measures
    • History of less than 1 year of menopause and not using adequate long-term antifertility measures
    • Using hormonal contraceptives
    • Using hormone replacement therapy
    • Unable to give assurance for protection against pregnancy for 3 months after the participation in this trial
    • Positive urine pregnancy test on the day of check-in (women of child bearing potential)
    • Positive serum β-human chorionic gonadotropin (hCG) level at the screening visit (women of child bearing potential)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: ZYDPLA1 tablet
ZYDPLA1 tablets: Route of administration: Oral Dosage (Single Ascending Study): 1 mg, 5mg, 20mg, 50mg, 100mg, 200mg Multiple Ascending Study: 100mg, 200mg Food effect and Gender effect study: 200mg
The oral dose of ZYDPLA1 tablet administered with 240 ± 10 mL of water at ambient temperature.
Placebo-vergelijker: Placebo
Placebo tablets: Route of administration: Oral Dosage (Single Ascending Study): 1 mg, 5mg, 20mg, 50mg, 100mg, 200mg Multiple Ascending Study: 100mg, 200mg Food effect and Gender effect study: 200mg
The oral dose of placebo tablet administered with 240 ± 10 mL of water at ambient temperature.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Tijdsspanne: 14 Days (Plan 1, III, and IV);
14 Days (Plan 1, III, and IV);
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Pharmacokinetic assessment: Maximum plasma concentration (Cmax)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Maximum plasma concentration (Cmax)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Time to reach maximum plasma concentration (Tmax)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Time to reach maximum plasma concentration (Tmax)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Terminal half life (t1/2)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Terminal half life (t1/2)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Elimination rate constant (λz)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Elimination rate constant (λz)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Clearance (CL)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Clearance (CL)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Volume of distribution (Vd)
Tijdsspanne: 14 Days (Plan I, III, and IV)
14 Days (Plan I, III, and IV)
Volume of distribution (Vd)
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Accumulation index
Tijdsspanne: 28 Days (Plan II)
28 Days (Plan II)
Pharmacodynamic effect (Plan I, III, and IV) assessment by monitoring primary parameters: Plasma DPPIV
Tijdsspanne: 14 Days
14 Days
Pharmacodynamic effect (Plan II) assessment by monitoring primary parameters: Plasma DPPIV
Tijdsspanne: 28 Days
28 Days
Glucagon-like peptide-1 (active and total)
Tijdsspanne: 14 Days
14 Days
Glucagon-like peptide-1 (active and total)
Tijdsspanne: 28 Days
28 Days
Secondary parameters: Plasma glucose
Tijdsspanne: 14 Days
14 Days
Plasma glucose
Tijdsspanne: 28 Days
28 Days
Serum insulin
Tijdsspanne: 14 Days
14 Days
Serum insulin
Tijdsspanne: 28 Days
28 Days
C-peptide
Tijdsspanne: 14 Days
14 Days
C-peptide
Tijdsspanne: 28 Days
28 Days
Glucagon
Tijdsspanne: 14 Days
14 Days
Glucagon
Tijdsspanne: 28 Days
28 Days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Studie directeur: Rajendrakumar H Jani, Ph.D.,, Zydus Lifesciences Limited

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 oktober 2014

Primaire voltooiing (Werkelijk)

1 oktober 2015

Studie voltooiing (Werkelijk)

1 oktober 2015

Studieregistratiedata

Eerst ingediend

24 november 2015

Eerst ingediend dat voldeed aan de QC-criteria

1 december 2015

Eerst geplaatst (Schatting)

3 december 2015

Updates van studierecords

Laatste update geplaatst (Schatting)

3 december 2015

Laatste update ingediend die voldeed aan QC-criteria

1 december 2015

Laatst geverifieerd

1 november 2015

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • ZYDPLA1 1001

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