A Phase IV, Open Label, 4-period Cross-over Study to Investigate a Drug Interaction Between Lamivudine and Sorbitol Oral Solutions in Healthy Volunteers

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02634073
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 16
• Location: 1
• Arms: 4
• Duration (Months): 2.3
• Patients Per Site Per Month: 7

Study Details

Study Description

Brief Summary

Lamivudine (3TC) is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children. Documented literature elucidates that simultaneous administration of multiple sorbitol-containing products could increase the potential for a significant interaction and may contribute to the lower 3TC exposures.

In this study several sorbitol doses (3.2 gram (g), 10.2 g, and 13.4 g solutions) will be administered with lamivudine to investigate dose dependency and mimic the situation where multiple sorbitol-containing antiretroviral medications may be co-administered with lamivudine. It will be open label, randomized, 4-way crossover (by William's design method) design at a single centre. Randomized participants will receive a single dose of each of four treatments after wash out period of minimum 7 days.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus	Drug: Lamivudine; Drug: Sorbitol	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Single-Center, 4-Period William's Cross-Over Design Drug Interaction Trial to Determine the Effects of Sorbitol-Containing Solutions on Lamivudine Exposure Following Administration of Lamivudine Oral Solution in Healthy Adult Subjects
• Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A: Lamivudine 300 milligram(mg) Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) after overnight fasting. Treatment period will be separated by at least 7 day wash out period.	Drug: Lamivudine; It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants
Experimental: Treatment B: Lamivudine 300 mg + Sorbitol 3.2 g (low dose) Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 3.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period.	Drug: Lamivudine; It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants; Drug: Sorbitol; It is a clear, colorless, odourless solution. It will be available in 3 dosage levels viz;. 3.2 g (low dose), 10.2 g (medium dose) and 13.4 g (high dose) sorbitol total dose.
Experimental: Treatment C: Lamivudine 300 mg + Sorbitol 10.2 g (medium dose) Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 10.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period	Drug: Lamivudine; It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants; Drug: Sorbitol; It is a clear, colorless, odourless solution. It will be available in 3 dosage levels viz;. 3.2 g (low dose), 10.2 g (medium dose) and 13.4 g (high dose) sorbitol total dose.
Experimental: Treatment D: Lamivudine 300 mg + Sorbitol 13.4 g (high dose) Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 13.4 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period	Drug: Lamivudine; It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants; Drug: Sorbitol; It is a clear, colorless, odourless solution. It will be available in 3 dosage levels viz;. 3.2 g (low dose), 10.2 g (medium dose) and 13.4 g (high dose) sorbitol total dose.

Outcome Measures

Primary Outcome Measures

1. Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24]) [Day 1 to Day 3 in each treatment period]

   Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.

2. Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct) [Day 1 to Day 3 in each treatment period]

   Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.

3. Lamivudine Elimination Half-life in Plasma (t1/2) [Day 1 to Day 3 in each treatment period]

   Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.

4. Plasma Lamivudine Apparent Oral Clearance (CL/F) [Day 1 to Day 3 in each treatment period]

   Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine CL/F

5. Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag) [Day 1 to Day 3 in each treatment period]

   Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period.

Secondary Outcome Measures

1. Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE) [Up to 5 Weeks]

   An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

2. Change From Baseline in Pulse Rate [Baseline and up to 5 weeks]

   Change from Baseline for pulse rate was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

3. Change From Baseline in Body Temperature [Baseline and up to 5 weeks]

   Change from Baseline for body temperature was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

4. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline and up to 5 weeks]

   Change from Baseline for DBP and SBP was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

5. Number of Participants With Treatment Emergent Laboratory Abnormality Grade [Up to Week 5]

   Division of Acquired immune deficiency syndrome (DAIDS) Table AE grades 1, 2, 3, and 4 of laboratory abnormalities were applied and grade were summarized by treatment and day and were listed by participant, treatment, day, and actual date and time. Treatment emergent grades are defined as any new toxicity grades or the worsened grades compared to Baseline grade. Treatment emergent lab abnormality Grade 1 for aspartate aminotransferase and sodium at follow-up visit are summarized.

6. Change From Baseline in Erythrocytes [Baseline and up to 5 weeks]

   Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for erythrocytes was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

7. Change From Baseline in Hematocrit [Baseline and up to 5 weeks]

   Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hematocrit was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

8. Change From Baseline in Hemoglobin [Baseline and up to 5 weeks]

   Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hemoglobin was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

9. Change From Baseline in Mean Corpuscular Hemoglobin (MCH) [Baseline and up to 5 weeks]

   Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCH was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

10. Change From Baseline in Mean Corpuscular Volume (MCV) [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCV was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

11. Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

12. Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for BUN, sodium, potassium, glucose, calcium were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

13. Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for AST, ALT and alkaline phosphatase were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

14. Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for creatinine and direct bilirubin were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Change from Baseline in total bilirubine was not assessed. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

15. Change From Baseline in Albumin [Baseline and up to 5 weeks]

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for albumin was calculated as the post-dose Visit Value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Between 18 and 65 years of age inclusive, at the time of signing the informed consent.

• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests.

• A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

• Body weight >=50 kilogram (kg) (110 pounds [lb]) for men and >45 kg (99 lb) for women and body mass index (BMI) within the range 18.5 - 31 kg/meter square (m^2) (inclusive).

• Male or Female. Females A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion Criteria:

• ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Participants with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Participants with a history of cholecystectomy, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.

• Corrected QT (QTc) interval according to Fridericia's formula (QTcF) > 450 milli-seconds (msec).

Notes:

1. The QTc is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.

2. The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.

3. For purposes of data analysis, Corrected QT interval according to Bazett's formula (QTcB), QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).

• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.

• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medications.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

• Creatinine clearance (CrCL) <60 mL/minutes (min).

• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• A positive pre-study drug/alcohol screen.

• A positive test for HIV antibody.

• Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days.

• The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Overland Park	Kansas	United States	66211

Sponsors and Collaborators

• ViiV Healthcare
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT02634073
• Other Study ID Numbers: 204857
• First Posted: Dec 17, 2015
• Last Update Posted: May 15, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by ViiV Healthcare: Lamivudine; Safety; Sorbitol; Pharmacokinetics
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Lamivudine; Sorbitol

Study Results

Participant Flow

Pre-assignment Detail	Sixteen subjects were randomized to one of the 4 treatment sequences separated by >=7 day washout between doses.

Arm/Group Title	Treatment Sequence 1: ADBC	Treatment Sequence 2: BACD	Treatment Sequence 3: CBDA	Treatment Sequence 4: DCAB
Arm/Group Description	Participants were randomized to receive a single dose of each of the four treatments where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g. All doses were administered after an overnight fast and there was >=7days washout between each period	Participants were randomized to receive a single dose of each of the four treatments where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g. All doses were administered after an overnight fast and there was >=7days washout between each period	Participants were randomized to receive a single dose of each of the four treatments where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g. All doses were administered after an overnight fast and there was >=7days washout between each period	Participants were randomized to receive a single dose of each of the four treatments where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g. All doses were administered after an overnight fast and there was >=7days washout between each period
Period Title: Overall Study
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Treatment Groups Combined
Arm/Group Description	Sixteen participants were randomized to receive one of the following 4 treatment sequences : Treatment sequence 1 : ABCD; Treatment sequence 2: DABC; Trearment sequence 3: BCDA; Treatment sequence 4: CDAB; where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g.
Overall Participants	16
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.6 (12.30)
Sex: Female, Male (Count of Participants)
Female	2 12.5%
Male	14 87.5%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	6 37.5%
White - White/Caucasian/European Heritage	10 62.5%

Outcome Measures

1. Primary Outcome

Title	Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])
Description	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.
Time Frame	Day 1 to Day 3 in each treatment period

Outcome Measure Data

Analysis Population Description

PK Summary Population: defined as participants who had valid lamivudine PK parameter estimates from both reference and test treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
AUC (0-inf); n=16, 14, 16, 13	13.2 (22.3)	11.3 (21.2)	8.93 (22.1)	8.60 (24.1)
AUC (0-24) ; n=16, 16, 16, 16	12.4 (23.6)	9.96 (22.6)	7.54 (23.7)	6.91 (28.9)
AUC (0-t) ; n=16, 16, 16, 16	12.9 (23.0)	10.6 (21.6)	8.21 (22.9)	7.55 (26.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.855
	Confidence Interval	(2-Sided) 90%; 0.799 to 0.914
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) comparison

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.677
	Confidence Interval	(2-Sided) 90%; 0.635 to 0.721
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) comparision

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.637
	Confidence Interval	(2-Sided) 90%; 0.594 to 0.682
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) comparision

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.803
	Confidence Interval	(2-Sided) 90%; 0.747 to 0.864
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-24) comparision

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.608
	Confidence Interval	(2-Sided) 90%; 0.566 to 0.655
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-24) comparision

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.557
	Confidence Interval	(2-Sided) 90%; 0.518 to 0.599
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-24) comparision

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.819
	Confidence Interval	(2-Sided) 90%; 0.766 to 0.876
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-t) comparision

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.636
	Confidence Interval	(2-Sided) 90%; 0.595 to 0.680
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-t) comparision

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.585
	Confidence Interval	(2-Sided) 90%; 0.548 to 0.626
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-t) comparision

2. Primary Outcome

Title	Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)
Description	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.
Time Frame	Day 1 to Day 3 in each treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
C24	0.036 (25.1)	0.036 (31.1)	0.041 (21.8)	0.039 (21.6)
Ct	0.013 (28.4)	0.017 (26.3)	0.019 (38.7)	0.018 (51.5)
Cmax	3.34 (34.9)	2.42 (32.7)	1.60 (27.2)	1.52 (30.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.993
	Confidence Interval	(2-Sided) 90%; 0.916 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	C24 comparison

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 90%; 1.03 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	C24 comparision

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 90%; 1.000 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	C24 comparision

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 90%; 1.13 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ct comparision

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 90%; 1.25 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ct comparision

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 90%; 1.18 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ct comparision

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.724
	Confidence Interval	(2-Sided) 90%; 0.657 to 0.798
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax comparision

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.479
	Confidence Interval	(2-Sided) 90%; 0.434 to 0.527
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax comparision

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.454
	Confidence Interval	(2-Sided) 90%; 0.412 to 0.500
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax comparision

3. Primary Outcome

Title	Lamivudine Elimination Half-life in Plasma (t1/2)
Description	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.
Time Frame	Day 1 to Day 3 in each treatment period

Outcome Measure Data

Analysis Population Description

PK Summary Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	14	16	13
Geometric Mean (Geometric Coefficient of Variation) [Hour (Hr)]	13.9 (20.9)	19.0 (40.6)	21.2 (47.3)	17.3 (48.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 90%; 1.11 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 90%; 1.25 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 90%; 1.04 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Plasma Lamivudine Apparent Oral Clearance (CL/F)
Description	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine CL/F
Time Frame	Day 1 to Day 3 in each treatment period

Outcome Measure Data

Analysis Population Description

PK Summary Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	14	16	13
Geometric Mean (Geometric Coefficient of Variation) [Liter (L)/hr]	22.738 (22.3)	26.621 (21.2)	33.608 (22.1)	34.875 (24.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, B: Lamivudine 300 mg + Sorbitol 3.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.170
	Confidence Interval	(2-Sided) 90%; 1.094 to 1.251
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, C: Lamivudine 300 mg + Sorbitol 10.2 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.478
	Confidence Interval	(2-Sided) 90%; 1.386 to 1.576
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Lamivudine 300 mg, D: Lamivudine 300 mg + Sorbitol 13.4 g
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.571
	Confidence Interval	(2-Sided) 90%; 1.466 to 1.684
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag)
Description	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period.
Time Frame	Day 1 to Day 3 in each treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
tmax	0.75	1.000	1.00	1.26
tlast	48.00	48.00	48.00	48.00
tlag	0.000	0.000	0.000	0.000

6. Secondary Outcome

Title	Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)
Description	An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
Time Frame	Up to 5 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population: defined as all participants who enrolled into the study and received at least one dose of study drug.

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
AEs	1 6.3%	2 NaN	1 NaN	1 NaN
SAEs	0 0%	0 NaN	0 NaN	0 NaN

7. Secondary Outcome

Title	Change From Baseline in Pulse Rate
Description	Change from Baseline for pulse rate was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population.Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3; n=15, 16, 16, 16	6.5 (3.42)	3.9 (14.3)	6.0 (6.86)	7.4 (8.57)
Follow up; n=16, 16, 16, 16	5.8 (6.41)	5.8 (6.41)	5.8 (6.41)	5.8 (6.41)

8. Secondary Outcome

Title	Change From Baseline in Body Temperature
Description	Change from Baseline for body temperature was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	0.03 (0.252)	0.07 (0.189)	0.08 (0.183)	-0.03 (0.145)
Follow up	-0.01 (0.365)	-0.01 (0.365)	-0.01 (0.365)	-0.01 (0.365)

9. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	Change from Baseline for DBP and SBP was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
DBP, Day 3; n=15, 16, 16, 16	5.1 (6.41)	4.5 (4.13)	2.1 (7.46)	5.6 (4.87)
DBP, Follow up; n=16, 16, 16, 16	4.6 (6.54)	4.6 (6.54)	4.6 (6.54)	4.6 (6.54)
SBP, Day 3; n=15, 16, 16, 16	3.6 (9.84)	3.1 (8.01)	5.1 (7.19)	5.3 (7.38)
SBP, Follow up; n=16, 16, 16, 16	7.4 (7.78)	7.4 (7.78)	7.4 (7.78)	7.4 (7.78)

10. Secondary Outcome

Title	Number of Participants With Treatment Emergent Laboratory Abnormality Grade
Description	Division of Acquired immune deficiency syndrome (DAIDS) Table AE grades 1, 2, 3, and 4 of laboratory abnormalities were applied and grade were summarized by treatment and day and were listed by participant, treatment, day, and actual date and time. Treatment emergent grades are defined as any new toxicity grades or the worsened grades compared to Baseline grade. Treatment emergent lab abnormality Grade 1 for aspartate aminotransferase and sodium at follow-up visit are summarized.
Time Frame	Up to Week 5

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Aspartate Aminotransferase	1 6.3%	1 NaN	1 NaN	1 NaN
Sodium	1 6.3%	1 NaN	1 NaN	1 NaN

11. Secondary Outcome

Title	Change From Baseline in Erythrocytes
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for erythrocytes was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	0.351 (0.298)	0.389 (0.200)	0.339 (0.257)	0.380 (0.243)
Follow up	0.142 (0.148)	0.142 (0.148)	0.142 (0.148)	0.142 (0.148)

12. Secondary Outcome

Title	Change From Baseline in Hematocrit
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hematocrit was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	0.0338 (0.02429)	0.0378 (0.02206)	0.0308 (0.01993)	0.0353 (0.01892)
Follow up	0.0091 (0.01254)	0.0091 (0.01254)	0.0091 (0.01254)	0.0091 (0.01254)

13. Secondary Outcome

Title	Change From Baseline in Hemoglobin
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hemoglobin was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	10.1 (8.05)	10.9 (5.26)	9.8 (6.44)	9.9 (5.83)
Follow up	3.4 (4.57)	3.4 (4.57)	3.4 (4.57)	3.4 (4.57)

14. Secondary Outcome

Title	Change From Baseline in Mean Corpuscular Hemoglobin (MCH)
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCH was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	0.02 (0.500)	-0.03 (0.419)	0.06 (0.403)	-0.24 (0.622)
Follow up	-0.14 (0.567)	-0.14 (0.567)	-0.14 (0.567)	-0.14 (0.567)

15. Secondary Outcome

Title	Change From Baseline in Mean Corpuscular Volume (MCV)
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCV was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	0.71 (1.95)	0.63 (1.89)	0.35 (2.06)	0.44 (1.54)
Follow up	-0.77 (1.55)	-0.77 (1.55)	-0.77 (1.55)	-0.77 (1.55)

16. Secondary Outcome

Title	Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Platelets, Day 3	19.2 (20.69)	13.9 (15.75)	13.8 (20.92)	6.1 (24.65)
Platelets, Follow up	2.3 (19.36)	2.3 (19.36)	2.3 (19.36)	2.3 (19.36)
Neutrophils, Day 3	0.35 (0.612)	0.42 (0.733)	0.53 (0.603)	0.31 (0.979)
Neutrophils, Follow up	-0.12 (0.717)	-0.12 (0.717)	-0.12 (0.717)	-0.12 (0.717)
Lymphocytes, Day 3	0.10 (0.432)	0.17 (0.338)	0.00 (0.446)	-0.03 (0.466)
Lymphocytes, Follow up	-0.08 (0.371)	-0.08 (0.371)	-0.08 (0.371)	-0.08 (0.371)
Monocytes, Day 3	0.01 (0.085)	0.03 (0.060)	-0.02 (0.122)	-0.01 (0.112)
Monocytes, Follow up	-0.08 (0.134)	-0.08 (0.134)	-0.08 (0.134)	-0.08 (0.134)
Eosinophils, Day 3	-0.03 (0.070)	-0.02 (0.075)	-0.04 (0.062)	-0.03 (0.070)
Eosinophils, Follow up	-0.01 (0.068)	-0.01 (0.068)	-0.01 (0.068)	-0.01 (0.068)
Basophils, Day 3	-0.01 (0.025)	0.00 (0.000)	-0.01 (0.025)	0.00 (0.037)
Basophils, Follow up	-0.01 (0.025)	-0.01 (0.025)	-0.01 (0.025)	-0.01 (0.025)

17. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for BUN, sodium, potassium, glucose, calcium were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
BUN, Day 3	-0.0892 (1.08675)	-0.5578 (0.93974)	0.0223 (1.05476)	0.0446 (1.38496)
BUN, Follow up	-0.4909 (1.00870)	-0.4909 (1.00870)	-0.4909 (1.00870)	-0.4909 (1.00870)
Sodium, Day 3	-2.4 (1.71)	-1.2 (1.42)	-2.6 (1.59)	-2.0 (1.63)
Sodium, Follow up	-0.1 (2.03)	-0.1 (2.03)	-0.1 (2.03)	-0.1 (2.03)
Potassium, Day 3	0.06 (0.418)	0.09 (0.481)	0.19 (0.382)	0.06 (0.386)
Potassium, Follow up	0.02 (0.387)	0.02 (0.387)	0.02 (0.387)	0.02 (0.387)
Glucose, Day 3	-0.05897 (0.496601)	0.05550 (0.342125)	0.01388 (0.342425)	-0.03122 (0.657300)
Glucose, Follow up	0.33994 (0.546377)	0.33994 (0.546377)	0.33994 (0.546377)	0.33994 (0.546377)
Calcium Day 3	0.0906 (0.11614)	0.1141 (0.08214)	0.1141 (0.07744)	0.0875 (0.07583)
Calcium, Follow up	0.0328 (0.05379)	0.0328 (0.05379)	0.0328 (0.05379)	0.0328 (0.05379)

18. Secondary Outcome

Title	Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for AST, ALT and alkaline phosphatase were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
AST, Day 3	-3.1 (4.84)	-3.5 (3.67)	-2.3 (2.44)	-19.1 (68.13)
AST, Follow up	1.1 (15.86)	1.1 (15.86)	1.1 (15.86)	1.1 (15.86)
ALT, Day 3	-2.2 (5.78)	-2.7 (4.16)	-2.2 (2.59)	-2.5 (7.05)
ALT, Follow up	0.4 (8.97)	0.4 (8.97)	0.4 (8.97)	0.4 (8.97)
Alkaline phosphatatse, Day 3	-0.4 (7.96)	1.1 (6.24)	1.5 (8.45)	-0.2 (7.37)
Alkaline phosphatase, Follow up	1.2 (7.01)	1.2 (7.01)	1.2 (7.01)	1.2 (7.01)

19. Secondary Outcome

Title	Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for creatinine and direct bilirubin were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Change from Baseline in total bilirubine was not assessed. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Creatinine, Day 3	3.86759 (9.112270)	2.21005 (6.847589)	4.42010 (7.217993)	0.55251 (6.011986)
Creatinine, Follow up	0.00000 (7.217993)	0.00000 (7.217993)	0.00000 (7.217993)	0.00000 (7.217993)
Direct bilirubin, Day 3	0.641 (0.8550)	0.107 (1.3200)	0.107 (0.7567)	0.321 (1.1202)
Direct bilirubin, Follow up	0.107 (1.4602)	0.107 (1.4602)	0.107 (1.4602)	0.107 (1.4602)

20. Secondary Outcome

Title	Change From Baseline in Albumin
Description	Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for albumin was calculated as the post-dose Visit Value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.
Time Frame	Baseline and up to 5 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	A: Lamivudine 300 mg	B: Lamivudine 300 mg + Sorbitol 3.2 g	C: Lamivudine 300 mg + Sorbitol 10.2 g	D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
Measure Participants	16	16	16	16
Day 3	1.8 (2.43)	2.3 (1.58)	2.1 (2.38)	2.1 (2.09)
Follow up	0.6 (1.63)	0.6 (1.63)	0.6 (1.63)	0.6 (1.63)

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 5 weeks).
Adverse Event Reporting Description	On-treatment SAEs and non-serious AEs are reported for Safety Population.
Arm/Group Title	A: Lamivudine 300 mg		B: Lamivudine 300 mg + Sorbitol 3.2 g		C: Lamivudine 300 mg + Sorbitol 10.2 g		D: Lamivudine 300 mg + Sorbitol 13.4 g
Arm/Group Description	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.		After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.		After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.		After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
All Cause Mortality
	A: Lamivudine 300 mg		B: Lamivudine 300 mg + Sorbitol 3.2 g		C: Lamivudine 300 mg + Sorbitol 10.2 g		D: Lamivudine 300 mg + Sorbitol 13.4 g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	A: Lamivudine 300 mg		B: Lamivudine 300 mg + Sorbitol 3.2 g		C: Lamivudine 300 mg + Sorbitol 10.2 g		D: Lamivudine 300 mg + Sorbitol 13.4 g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	A: Lamivudine 300 mg		B: Lamivudine 300 mg + Sorbitol 3.2 g		C: Lamivudine 300 mg + Sorbitol 10.2 g		D: Lamivudine 300 mg + Sorbitol 13.4 g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		2/16 (12.5%)		1/16 (6.3%)		1/16 (6.3%)
General disorders
Vessel puncture site pain	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Infections and infestations
Gastroenteritis	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Vaginal infection	0/16 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Myalgia	1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Nervous system disorders
Dizziness	0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.