Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PKs) of ZYDPLA1 Following Oral Administration in Healthy Volunteers
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
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
California
-
Chula Vista、California、アメリカ、91911
- Profil Institute for Clinical Research
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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)
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ: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.
|
|
プラセボコンパレーター: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.
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
時間枠: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.
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Pharmacokinetic assessment: Maximum plasma concentration (Cmax)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Maximum plasma concentration (Cmax)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Time to reach maximum plasma concentration (Tmax)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Time to reach maximum plasma concentration (Tmax)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
時間枠: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)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
時間枠: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)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Terminal half life (t1/2)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Terminal half life (t1/2)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Elimination rate constant (λz)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Elimination rate constant (λz)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Clearance (CL)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Clearance (CL)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Volume of distribution (Vd)
時間枠:14 Days (Plan I, III, and IV)
|
14 Days (Plan I, III, and IV)
|
|
Volume of distribution (Vd)
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Accumulation index
時間枠:28 Days (Plan II)
|
28 Days (Plan II)
|
|
Pharmacodynamic effect (Plan I, III, and IV) assessment by monitoring primary parameters: Plasma DPPIV
時間枠:14 Days
|
14 Days
|
|
Pharmacodynamic effect (Plan II) assessment by monitoring primary parameters: Plasma DPPIV
時間枠:28 Days
|
28 Days
|
|
Glucagon-like peptide-1 (active and total)
時間枠:14 Days
|
14 Days
|
|
Glucagon-like peptide-1 (active and total)
時間枠:28 Days
|
28 Days
|
|
Secondary parameters: Plasma glucose
時間枠:14 Days
|
14 Days
|
|
Plasma glucose
時間枠:28 Days
|
28 Days
|
|
Serum insulin
時間枠:14 Days
|
14 Days
|
|
Serum insulin
時間枠:28 Days
|
28 Days
|
|
C-peptide
時間枠:14 Days
|
14 Days
|
|
C-peptide
時間枠:28 Days
|
28 Days
|
|
Glucagon
時間枠:14 Days
|
14 Days
|
|
Glucagon
時間枠:28 Days
|
28 Days
|
協力者と研究者
捜査官
- スタディディレクター:Rajendrakumar H Jani, Ph.D.,、Zydus Lifesciences Limited
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。