Diabetes MellitusPhase 1NCT02620592
Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PKs) of ZYDPLA1 Following Oral Administration in Healthy Volunteers
A Phase 1 study testing ZYDPLA1 tablet in people with Diabetes Mellitus, run by Zydus Lifesciences Limited at 1 site in United States.
Trial summary
This First in Human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYDPLA1 in normal healthy adult volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- ZYDPLA1 tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Oct 2015
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male or female between 18 and 65 years of age.
- 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.
- 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).
- Capable of giving written informed consent, which includes compliance with protocol.
- Corrected QT interval (QTc) interval < 450msec (as measured by QTcF)
- 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.
- 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.
Who cannot join
- Presence or history of pancreatitis at any time {Serum Amylase/Serum Lipase more than significant upper normal limit (≥1.5 times UNL)}
- Presence or history of severe gastrointestinal disease in the last 6 months
- Presence or history of renal insufficiency at any time {Serum creatinine more than upper normal limit (UNL)}
- Active liver disease and/or liver transaminases greater than 1.5 times UNL
- 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)
- History or presence of any medication in the last 14 days
Show all 29Show fewer
- History or presence of significant alcoholism or drug abuse within the past 1 year
- History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day)
- Difficulty with donating blood or difficulty in accessibility of veins.
- Intolerance to venipuncture.
- Systolic blood pressure more than 150 mmHg and less than 100 mmHg and diastolic blood pressure more than 90 mmHg
- Pulse rate less than 50/minute and more than 100/minute
- Any clinically significant laboratory findings during screening
- History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening as determined by the Principal Investigator.
- Major illness and/or major surgery in last 3 months
- 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).
- Volunteers who have donated one unit (450 mL) of blood in the past 3 months
- Positive Alcohol breath analyzer at the time of Screening and Check-in
- A positive hepatitis screen (includes subtype B and C) and/or a positive test result for HIV antibody.
- 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.
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Profil Institute for Clinical Research
Chula Vista, California, 91911
About this study
Official title: 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.
Read the detailed description
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:
- single dose escalation study ii) multiple dose escalation study, iii) gender effect study and iv) food effect study.
- Conditions
- Diabetes Mellitus
- Being tested
- ZYDPLA1 tablet, Placebo tablet
- Keywords
- Healthy Subject, ZYDPLA1, DPPIV inhibitor, Pharmacokinetics, Safety
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZYDPLA1 tabletDrug
The oral dose of ZYDPLA1 tablet administered with 240 ± 10 mL of water at ambient temperature.
Placebo tabletDrug
The oral dose of placebo tablet administered with 240 ± 10 mL of water at ambient temperature.
| Study group | Role | What they receive |
|---|---|---|
| ZYDPLA1 tablet | Active comparator | 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 Receives: Drug: ZYDPLA1 tablet |
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Measured: 14 Days (Plan 1, III, and IV);
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Measured: 28 Days (Plan II)
Secondary outcomes (29)
Pharmacokinetic assessment: Maximum plasma concentration (Cmax)
Measured: 14 Days (Plan I, III, and IV)
Maximum plasma concentration (Cmax)
Measured: 28 Days (Plan II)
Time to reach maximum plasma concentration (Tmax)
Measured: 14 Days (Plan I, III, and IV)
Time to reach maximum plasma concentration (Tmax)
Measured: 28 Days (Plan II)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Measured: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Measured: 28 Days (Plan II)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Measured: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Measured: 28 Days (Plan II)
Terminal half life (t1/2)
Measured: 14 Days (Plan I, III, and IV)
Terminal half life (t1/2)
Measured: 28 Days (Plan II)
Elimination rate constant (λz)
Measured: 14 Days (Plan I, III, and IV)
Elimination rate constant (λz)
Measured: 28 Days (Plan II)
Clearance (CL)
Measured: 14 Days (Plan I, III, and IV)
Clearance (CL)
Measured: 28 Days (Plan II)
Volume of distribution (Vd)
Measured: 14 Days (Plan I, III, and IV)
Volume of distribution (Vd)
Measured: 28 Days (Plan II)
Accumulation index
Measured: 28 Days (Plan II)
Pharmacodynamic effect (Plan I, III, and IV) assessment by monitoring primary parameters: Plasma DPPIV
Measured: 14 Days
Pharmacodynamic effect (Plan II) assessment by monitoring primary parameters: Plasma DPPIV
Measured: 28 Days
Glucagon-like peptide-1 (active and total)
Measured: 14 Days
Glucagon-like peptide-1 (active and total)
Measured: 28 Days
Secondary parameters: Plasma glucose
Measured: 14 Days
Plasma glucose
Measured: 28 Days
Serum insulin
Measured: 14 Days
Serum insulin
Measured: 28 Days
C-peptide
Measured: 14 Days
C-peptide
Measured: 28 Days
Glucagon
Measured: 14 Days
Glucagon
Measured: 28 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2015 (estimated)
- Study startOct 2014
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zydus Lifesciences Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rajendrakumar H Jani, Ph.D.,, Study director, Zydus Lifesciences Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620592
- Sponsor's protocol ID
- ZYDPLA1 1001
- Status last verified
- Nov 2015
- First submitted
- 24 Nov 2015
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02620592
- Acronym / sponsor ID
- ZYDPLA1 1001
- Conditions
- Diabetes Mellitus
- Keywords
- Healthy Subject, ZYDPLA1, DPPIV inhibitor, Pharmacokinetics, Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Zydus Lifesciences LimitedIndustry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 3 Dec 2015 (estimated)
- 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.
This First in Human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYDPLA1 in normal healthy adult volunteers.
Detailed description
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:
- single dose escalation study ii) multiple dose escalation study, iii) gender effect study and iv) food effect study.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZYDPLA1 tablet | Active comparator | Drug: ZYDPLA1 tabletZYDPLA1 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 |
| Placebo | Placebo comparator | Drug: Placebo tabletPlacebo 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy male or female between 18 and 65 years of age.
- 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.
- 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).
- Capable of giving written informed consent, which includes compliance with protocol.
- Corrected QT interval (QTc) interval < 450msec (as measured by QTcF)
Key exclusion criteria (29 listed)
- Presence or history of pancreatitis at any time {Serum Amylase/Serum Lipase more than significant upper normal limit (≥1.5 times UNL)}
- Presence or history of severe gastrointestinal disease in the last 6 months
- Presence or history of renal insufficiency at any time {Serum creatinine more than upper normal limit (UNL)}
- Active liver disease and/or liver transaminases greater than 1.5 times UNL
- 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)
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 |
|---|---|---|
| ZYDPLA1 tabletThe oral dose of ZYDPLA1 tablet administered with 240 ± 10 mL of water at ambient temperature. | Drug | ZYDPLA1 tablet |
| Placebo tabletThe oral dose of placebo tablet administered with 240 ± 10 mL of water at ambient temperature. | Drug | Placebo |
Primary outcome
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Time frame: 14 Days (Plan 1, III, and IV);
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Time frame: 28 Days (Plan II)
29 secondary outcomes
Pharmacokinetic assessment: Maximum plasma concentration (Cmax)
Time frame: 14 Days (Plan I, III, and IV)
Maximum plasma concentration (Cmax)
Time frame: 28 Days (Plan II)
Time to reach maximum plasma concentration (Tmax)
Time frame: 14 Days (Plan I, III, and IV)
Time to reach maximum plasma concentration (Tmax)
Time frame: 28 Days (Plan II)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time frame: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time frame: 28 Days (Plan II)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Time frame: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Time frame: 28 Days (Plan II)
Terminal half life (t1/2)
Time frame: 14 Days (Plan I, III, and IV)
Terminal half life (t1/2)
Time frame: 28 Days (Plan II)
Elimination rate constant (λz)
Time frame: 14 Days (Plan I, III, and IV)
Elimination rate constant (λz)
Time frame: 28 Days (Plan II)
Clearance (CL)
Time frame: 14 Days (Plan I, III, and IV)
Clearance (CL)
Time frame: 28 Days (Plan II)
Volume of distribution (Vd)
Time frame: 14 Days (Plan I, III, and IV)
Volume of distribution (Vd)
Time frame: 28 Days (Plan II)
Accumulation index
Time frame: 28 Days (Plan II)
Pharmacodynamic effect (Plan I, III, and IV) assessment by monitoring primary parameters: Plasma DPPIV
Time frame: 14 Days
Pharmacodynamic effect (Plan II) assessment by monitoring primary parameters: Plasma DPPIV
Time frame: 28 Days
Glucagon-like peptide-1 (active and total)
Time frame: 14 Days
Glucagon-like peptide-1 (active and total)
Time frame: 28 Days
Secondary parameters: Plasma glucose
Time frame: 14 Days
Plasma glucose
Time frame: 28 Days
Serum insulin
Time frame: 14 Days
Serum insulin
Time frame: 28 Days
C-peptide
Time frame: 14 Days
C-peptide
Time frame: 28 Days
Glucagon
Time frame: 14 Days
Glucagon
Time frame: 28 Days
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 3 Dec 2015.
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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.
Rajendrakumar H Jani, Ph.D., study director
Zydus Lifesciences Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZYDPLA1 tablet in people with Diabetes Mellitus, run by Zydus Lifesciences Limited at 1 site in United States.
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 29 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 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations. (time frame: 14 Days (Plan 1, III, and IV);). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Dec 2015.