A Phase III Study to Evaluate the Safety and Pharmacokinetics of MethylcobalaminNasal Spray, 500μg (Torrent Pharmaceuticals) and Compare the Efficacy ofMethylcobalamin Nasal Spray, 500μg (Torrent Pharmaceuticals) with NasoB12, 500μg(Troikaa Pharmaceuticals)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 249
- 试验地点
- 20
- 主要终点
- Part A:
研究概览
简要总结
Efficacy of methylcobalamin administered via oral or parenteral route has been established in various neurological and haematological disorders associated with vitamin B12 deficiency.
Recently, methylcobalamin has been approved for administration via nasal route as well. Torrent Pharmaceuticals has developed a new formulation of methylcobalamin for administration as a nasal spray.
Based on preclinical exposure and safety data, Torrent Pharmaceuticals proposes to carry out a phase III study to evaluate the safety, tolerability, pharmacokinetic profile and efficacy of its
new formulation methylcobalamin nasal spray. As the efficacy of methylcobalamin is already proven, phase II studies are not required. This study is proposed to be conducted in two parts. After
ascertaining the safety and determining the systemic exposure in first part (Part A), Torrent Pharmaceuticals proposes to evaluate the efficacy and safety of methylcobalamin nasal spray in the second part
(Part B) of the Phase III study. Part A study will be done in healthy subjects, and in Part B study, patients who have subclinical vitamin B12 deficiency will be selected. Part B will commence after
ascertaining the safety of the new formulation and determining the human dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Part A Inclusion Criteria
- •Male or female subjects of 18-45 years of age
- •Subject voluntarily give written informed consent to participate in the study.
- •Part B Inclusion Criteria
- •Patient with serum vitamin B12 levels <200pg/mL 3.
排除标准
- •Part A:Exclusion Criteria
- •Subject with a history of hypersensitivity to intranasal administration of vitamin B12 or its excipients or any intranasal preparations.
- •Subject who have taken any medication by intranasal route or have used any vitamin supplement within the past 72 hours prior to screening.
- •History of consumption of vitamin supplements i.e. as prescribed medication in the last 14 Days or over-the-counter medication/ herbal remedies in the last 7 Days prior to screening.
- •Subjects currently on treatment with drugs, which interfere with folate or folic acid metabolism and serum vitamin B12 assay (e.g., cholestyramine, methotrexate, pyrimethamine, proton pump inhibitors, trimethoprim, etc.)
- •Subject with clinically significant abnormal nasal or respiratory tract conditions, for example, atrophic rhinitis, nasal polyp, upper respiratory tract infection etc.
- •which may alter the absorption of the study investigational product.
- •Subject having any clinically significant medical illness that would compromise safety of the subject or study outcome/serum vitamin B12 levels as per investigator opinion
- •Subjects with liver enzymes (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase) > 2.5X the upper limit of normal value (ULN) or total bilirubin >1.5X of ULN or serum creatinine >1.5X of ULN at screening and considered clinically significant by the investigator.
- •History of alcohol or drug abuse or tobacco sniffing.
- •Subjects with known cases of haemoglobinopathies (e.g history of thalessemia minor/major, sickle cell anemia etc.).
- •Subject with clinically abnormal findings on physical examination, vital signs, electrocardiogram and laboratoryinvestigations at screening
- •Subjects positive for Hepatitis B surface antigen (HBsAg),Hepatitis C antibody and human immunodeficiency virus (HIV)antibody test.
- •Subject with positive breath-alcohol test at enrolment.
- •Subject with positive opiate, tetrahydrocannabinol (THC),amphetamine, barbiturates, benzodiazepines or cocaine on urine test at enrolment or known active alcohol abuse within past 6 months
- •Pregnant or lactating women.
- •In the opinion of the investigator, subject is either unable to cooperate or unlikely to adhere with any study procedure
- •Subjects who have participated in any other investigational drug trial within the past 3 months prior to screening.
- •Part B:Exclusion Criteria
- •Patients with a history of hypersensitivity to intranasal administration of vitamin B12 or its excipients or any intranasal preparations.
- •Patients who have taken any medication by intranasal route or have used any vitamin supplement within the past 72 hours prior to screening.
- •Patients having any clinically significant medical illness that would compromise safety of the patient or study outcome/serum vitamin B12 levels as per investigator opinion
- •Patients who are known seropositive cases of HIV, Hepatitis B or Hepatitis C.
- •Patients with history of recurrent or current abuse of alcohol and drugs of abuse.
结局指标
主要结局
Part A:
时间窗: Proportion of patients achieving, serum vitamin B12 levels more than 200 pg/mL at Day 14
1) To evaluate the safety and tolerability of methylcobalamin nasal spray in healthy subjects
时间窗: Proportion of patients achieving, serum vitamin B12 levels more than 200 pg/mL at Day 14
2)To study serum concentration v/s time of methylcobalamin nasal spray to guide dosing in Part B
时间窗: Proportion of patients achieving, serum vitamin B12 levels more than 200 pg/mL at Day 14
Part B:
时间窗: Proportion of patients achieving, serum vitamin B12 levels more than 200 pg/mL at Day 14
1) Proportion of patients achieving, serum vitamin B12 levels 200 pg/mL at Day 14
时间窗: Proportion of patients achieving, serum vitamin B12 levels more than 200 pg/mL at Day 14
次要结局
- Part B:Proportion of patients maintaining serum vitamin B12 level 200 pg/mL at the end of 2 weeks of being on maintenance dose (Day 28) in each treatment group
- Methylmalonic acid (MMA) levels as compared to baseline at(Day 7 and 14 in each treatment group)
- Reticulocyte count and Reticulocyte Production Index (RPI) as(compared to baseline at Day 7 and 14 in each treatment group)
- Proportion of patients achieving serum vitamin B12 level 200(pg/mL at Day 21 in each treatment group)
- Nasal sensory evaluation questionnaire score at Day 14(Day 14)
- Total amount of vitamin B12 excreted in urine over 12 hours’(time after first dose)